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. 1996 Sep 15;318(Pt 3):729–747. doi: 10.1042/bj3180729

Signal-transducing protein phosphorylation cascades mediated by Ras/Rho proteins in the mammalian cell: the potential for multiplex signalling.

D T Denhardt 1
PMCID: PMC1217680  PMID: 8836113

Abstract

The features of three distinct protein phosphorylation cascades in mammalian cells are becoming clear. These signalling pathways link receptor-mediated events at the cell surface or intracellular perturbations such as DNA damage to changes in cytoskeletal structure, vesicle transport and altered transcription factor activity. The best known pathway, the Ras-->Raf-->MEK-->ERK cascade [where ERK is extracellular-signal-regulated kinase and MEK is mitogen-activated protein (MAP) kinase/ERK kinase], is typically stimulated strongly by mitogens and growth factors. The other two pathways, stimulated primarily by assorted cytokines, hormones and various forms of stress, predominantly utilize p21 proteins of the Rho family (Rho, Rac and CDC42), although Ras can also participate. Diagnostic of each pathway is the MAP kinase component, which is phosphorylated by a unique dual-specificity kinase on both tyrosine and threonine in one of three motifs (Thr-Glu-Tyr, Thr-Phe-Tyr or Thr-Gly-Tyr), depending upon the pathway. In addition to activating one or more protein phosphorylation cascades, the initiating stimulus may also mobilize a variety of other signalling molecules (e.g. protein kinase C isoforms, phospholipid kinases, G-protein alpha and beta gamma subunits, phospholipases, intracellular Ca2+). These various signals impact to a greater or lesser extent on multiple downstream effectors. Important concepts are that signal transmission often entails the targeted relocation of specific proteins in the cell, and the reversible formation of protein complexes by means of regulated protein phosphorylation. The signalling circuits may be completed by the phosphorylation of upstream effectors by downstream kinases, resulting in a modulation of the signal. Signalling is terminated and the components returned to the ground state largely by dephosphorylation. There is an indeterminant amount of cross-talk among the pathways, and many of the proteins in the pathways belong to families of closely related proteins. The potential for more than one signal to be conveyed down a pathway simultaneously (multiplex signalling) is discussed. The net effect of a given stimulus on the cell is the result of a complex intracellular integration of the intensity and duration of activation of the individual pathways. The specific outcome depends on the particular signalling molecules expressed by the target cells and on the dynamic balance among the pathways.

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Selected References

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  1. Abrams C. S., Wu H., Zhao W., Belmonte E., White D., Brass L. F. Pleckstrin inhibits phosphoinositide hydrolysis initiated by G-protein-coupled and growth factor receptors. A role for pleckstrin's PH domains. J Biol Chem. 1995 Jun 16;270(24):14485–14492. doi: 10.1074/jbc.270.24.14485. [DOI] [PubMed] [Google Scholar]
  2. Acs P., Szallasi Z., Kazanietz M. G., Blumberg P. M. Differential activation of PKC isozymes by 14-3-3 zeta protein. Biochem Biophys Res Commun. 1995 Nov 2;216(1):103–109. doi: 10.1006/bbrc.1995.2597. [DOI] [PubMed] [Google Scholar]
  3. Adachi M., Fischer E. H., Ihle J., Imai K., Jirik F., Neel B., Pawson T., Shen S., Thomas M., Ullrich A. Mammalian SH2-containing protein tyrosine phosphatases. Cell. 1996 Apr 5;85(1):15–15. doi: 10.1016/s0092-8674(00)81077-6. [DOI] [PubMed] [Google Scholar]
  4. Aitken A. 14-3-3 proteins on the MAP. Trends Biochem Sci. 1995 Mar;20(3):95–97. doi: 10.1016/s0968-0004(00)88971-9. [DOI] [PubMed] [Google Scholar]
  5. Aronheim A., Engelberg D., Li N., al-Alawi N., Schlessinger J., Karin M. Membrane targeting of the nucleotide exchange factor Sos is sufficient for activating the Ras signaling pathway. Cell. 1994 Sep 23;78(6):949–961. doi: 10.1016/0092-8674(94)90271-2. [DOI] [PubMed] [Google Scholar]
  6. Bagrodia S., Dérijard B., Davis R. J., Cerione R. A. Cdc42 and PAK-mediated signaling leads to Jun kinase and p38 mitogen-activated protein kinase activation. J Biol Chem. 1995 Nov 24;270(47):27995–27998. doi: 10.1074/jbc.270.47.27995. [DOI] [PubMed] [Google Scholar]
  7. Barford D. Protein phosphatases. Curr Opin Struct Biol. 1995 Dec;5(6):728–734. doi: 10.1016/0959-440x(95)80004-2. [DOI] [PubMed] [Google Scholar]
  8. Ben-Levy R., Leighton I. A., Doza Y. N., Attwood P., Morrice N., Marshall C. J., Cohen P. Identification of novel phosphorylation sites required for activation of MAPKAP kinase-2. EMBO J. 1995 Dec 1;14(23):5920–5930. doi: 10.1002/j.1460-2075.1995.tb00280.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bird T. A., Kyriakis J. M., Tyshler L., Gayle M., Milne A., Virca G. D. Interleukin-1 activates p54 mitogen-activated protein (MAP) kinase/stress-activated protein kinase by a pathway that is independent of p21ras, Raf-1, and MAP kinase kinase. J Biol Chem. 1994 Dec 16;269(50):31836–31844. [PubMed] [Google Scholar]
  10. Bjørkøy G., Overvatn A., Diaz-Meco M. T., Moscat J., Johansen T. Evidence for a bifurcation of the mitogenic signaling pathway activated by Ras and phosphatidylcholine-hydrolyzing phospholipase C. J Biol Chem. 1995 Sep 8;270(36):21299–21306. doi: 10.1074/jbc.270.36.21299. [DOI] [PubMed] [Google Scholar]
  11. Blaikie P., Immanuel D., Wu J., Li N., Yajnik V., Margolis B. A region in Shc distinct from the SH2 domain can bind tyrosine-phosphorylated growth factor receptors. J Biol Chem. 1994 Dec 23;269(51):32031–32034. [PubMed] [Google Scholar]
  12. Blank J. L., Gerwins P., Elliott E. M., Sather S., Johnson G. L. Molecular cloning of mitogen-activated protein/ERK kinase kinases (MEKK) 2 and 3. Regulation of sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase. J Biol Chem. 1996 Mar 8;271(10):5361–5368. doi: 10.1074/jbc.271.10.5361. [DOI] [PubMed] [Google Scholar]
  13. Blenis J. Signal transduction via the MAP kinases: proceed at your own RSK. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5889–5892. doi: 10.1073/pnas.90.13.5889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Bonnefoy-Bérard N., Liu Y. C., von Willebrand M., Sung A., Elly C., Mustelin T., Yoshida H., Ishizaka K., Altman A. Inhibition of phosphatidylinositol 3-kinase activity by association with 14-3-3 proteins in T cells. Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10142–10146. doi: 10.1073/pnas.92.22.10142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Bork P., Margolis B. A phosphotyrosine interaction domain. Cell. 1995 Mar 10;80(5):693–694. doi: 10.1016/0092-8674(95)90347-x. [DOI] [PubMed] [Google Scholar]
  16. Bortner D. M., Langer S. J., Ostrowski M. C. Non-nuclear oncogenes and the regulation of gene expression in transformed cells. Crit Rev Oncog. 1993;4(2):137–160. [PubMed] [Google Scholar]
  17. Braselmann S., McCormick F. Bcr and Raf form a complex in vivo via 14-3-3 proteins. EMBO J. 1995 Oct 2;14(19):4839–4848. doi: 10.1002/j.1460-2075.1995.tb00165.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Buday L., Warne P. H., Downward J. Downregulation of the Ras activation pathway by MAP kinase phosphorylation of Sos. Oncogene. 1995 Oct 5;11(7):1327–1331. [PubMed] [Google Scholar]
  19. Burgering B. M., Bos J. L. Regulation of Ras-mediated signalling: more than one way to skin a cat. Trends Biochem Sci. 1995 Jan;20(1):18–22. doi: 10.1016/s0968-0004(00)88944-6. [DOI] [PubMed] [Google Scholar]
  20. Burgering B. M., de Vries-Smits A. M., Medema R. H., van Weeren P. C., Tertoolen L. G., Bos J. L. Epidermal growth factor induces phosphorylation of extracellular signal-regulated kinase 2 via multiple pathways. Mol Cell Biol. 1993 Dec;13(12):7248–7256. doi: 10.1128/mcb.13.12.7248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Böhm M., Moellmann G., Cheng E., Alvarez-Franco M., Wagner S., Sassone-Corsi P., Halaban R. Identification of p90RSK as the probable CREB-Ser133 kinase in human melanocytes. Cell Growth Differ. 1995 Mar;6(3):291–302. [PubMed] [Google Scholar]
  22. Büscher D., Hipskind R. A., Krautwald S., Reimann T., Baccarini M. Ras-dependent and -independent pathways target the mitogen-activated protein kinase network in macrophages. Mol Cell Biol. 1995 Jan;15(1):466–475. doi: 10.1128/mcb.15.1.466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Cano E., Mahadevan L. C. Parallel signal processing among mammalian MAPKs. Trends Biochem Sci. 1995 Mar;20(3):117–122. doi: 10.1016/s0968-0004(00)88978-1. [DOI] [PubMed] [Google Scholar]
  24. Cantor S. B., Urano T., Feig L. A. Identification and characterization of Ral-binding protein 1, a potential downstream target of Ral GTPases. Mol Cell Biol. 1995 Aug;15(8):4578–4584. doi: 10.1128/mcb.15.8.4578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Catling A. D., Schaeffer H. J., Reuter C. W., Reddy G. R., Weber M. J. A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and regulates MEK function. Mol Cell Biol. 1995 Oct;15(10):5214–5225. doi: 10.1128/mcb.15.10.5214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Cavigelli M., Dolfi F., Claret F. X., Karin M. Induction of c-fos expression through JNK-mediated TCF/Elk-1 phosphorylation. EMBO J. 1995 Dec 1;14(23):5957–5964. doi: 10.1002/j.1460-2075.1995.tb00284.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Chambers A. F., Tuck A. B. Ras-responsive genes and tumor metastasis. Crit Rev Oncog. 1993;4(2):95–114. [PubMed] [Google Scholar]
  28. Chant J., Stowers L. GTPase cascades choreographing cellular behavior: movement, morphogenesis, and more. Cell. 1995 Apr 7;81(1):1–4. doi: 10.1016/0092-8674(95)90363-1. [DOI] [PubMed] [Google Scholar]
  29. Chatani Y., Tanimura S., Miyoshi N., Hattori A., Sato M., Kohno M. Cell type-specific modulation of cell growth by transforming growth factor beta 1 does not correlate with mitogen-activated protein kinase activation. J Biol Chem. 1995 Dec 22;270(51):30686–30692. doi: 10.1074/jbc.270.51.30686. [DOI] [PubMed] [Google Scholar]
  30. Chen Q., Kinch M. S., Lin T. H., Burridge K., Juliano R. L. Integrin-mediated cell adhesion activates mitogen-activated protein kinases. J Biol Chem. 1994 Oct 28;269(43):26602–26605. [PubMed] [Google Scholar]
  31. Chen Q., Olashaw N., Wu J. Participation of reactive oxygen species in the lysophosphatidic acid-stimulated mitogen-activated protein kinase kinase activation pathway. J Biol Chem. 1995 Dec 1;270(48):28499–28502. doi: 10.1074/jbc.270.48.28499. [DOI] [PubMed] [Google Scholar]
  32. Cherniack A. D., Klarlund J. K., Conway B. R., Czech M. P. Disassembly of Son-of-sevenless proteins from Grb2 during p21ras desensitization by insulin. J Biol Chem. 1995 Jan 27;270(4):1485–1488. [PubMed] [Google Scholar]
  33. Chou M. M., Blenis J. The 70 kDa S6 kinase: regulation of a kinase with multiple roles in mitogenic signalling. Curr Opin Cell Biol. 1995 Dec;7(6):806–814. doi: 10.1016/0955-0674(95)80064-6. [DOI] [PubMed] [Google Scholar]
  34. Chuang C. F., Ng S. Y. Functional divergence of the MAP kinase pathway. ERK1 and ERK2 activate specific transcription factors. FEBS Lett. 1994 Jun 13;346(2-3):229–234. doi: 10.1016/0014-5793(94)00480-3. [DOI] [PubMed] [Google Scholar]
  35. Chuang T. H., Xu X., Kaartinen V., Heisterkamp N., Groffen J., Bokoch G. M. Abr and Bcr are multifunctional regulators of the Rho GTP-binding protein family. Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10282–10286. doi: 10.1073/pnas.92.22.10282. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Claesson-Welsh L. Platelet-derived growth factor receptor signals. J Biol Chem. 1994 Dec 23;269(51):32023–32026. [PubMed] [Google Scholar]
  37. Cobb M. H., Goldsmith E. J. How MAP kinases are regulated. J Biol Chem. 1995 Jun 23;270(25):14843–14846. doi: 10.1074/jbc.270.25.14843. [DOI] [PubMed] [Google Scholar]
  38. Coso O. A., Chiariello M., Kalinec G., Kyriakis J. M., Woodgett J., Gutkind J. S. Transforming G protein-coupled receptors potently activate JNK (SAPK). Evidence for a divergence from the tyrosine kinase signaling pathway. J Biol Chem. 1995 Mar 10;270(10):5620–5624. doi: 10.1074/jbc.270.10.5620. [DOI] [PubMed] [Google Scholar]
  39. Coso O. A., Chiariello M., Yu J. C., Teramoto H., Crespo P., Xu N., Miki T., Gutkind J. S. The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell. 1995 Jun 30;81(7):1137–1146. doi: 10.1016/s0092-8674(05)80018-2. [DOI] [PubMed] [Google Scholar]
  40. Cowley S., Paterson H., Kemp P., Marshall C. J. Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells. Cell. 1994 Jun 17;77(6):841–852. doi: 10.1016/0092-8674(94)90133-3. [DOI] [PubMed] [Google Scholar]
  41. Crespo P., Cachero T. G., Xu N., Gutkind J. S. Dual effect of beta-adrenergic receptors on mitogen-activated protein kinase. Evidence for a beta gamma-dependent activation and a G alpha s-cAMP-mediated inhibition. J Biol Chem. 1995 Oct 20;270(42):25259–25265. doi: 10.1074/jbc.270.42.25259. [DOI] [PubMed] [Google Scholar]
  42. Crespo P., Xu N., Simonds W. F., Gutkind J. S. Ras-dependent activation of MAP kinase pathway mediated by G-protein beta gamma subunits. Nature. 1994 Jun 2;369(6479):418–420. doi: 10.1038/369418a0. [DOI] [PubMed] [Google Scholar]
  43. Cross D. A., Alessi D. R., Cohen P., Andjelkovich M., Hemmings B. A. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 1995 Dec 21;378(6559):785–789. doi: 10.1038/378785a0. [DOI] [PubMed] [Google Scholar]
  44. Cullen P. J., Hsuan J. J., Truong O., Letcher A. J., Jackson T. R., Dawson A. P., Irvine R. F. Identification of a specific Ins(1,3,4,5)P4-binding protein as a member of the GAP1 family. Nature. 1995 Aug 10;376(6540):527–530. doi: 10.1038/376527a0. [DOI] [PubMed] [Google Scholar]
  45. Dalton S., Treisman R. Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element. Cell. 1992 Feb 7;68(3):597–612. doi: 10.1016/0092-8674(92)90194-h. [DOI] [PubMed] [Google Scholar]
  46. Daum G., Eisenmann-Tappe I., Fries H. W., Troppmair J., Rapp U. R. The ins and outs of Raf kinases. Trends Biochem Sci. 1994 Nov;19(11):474–480. doi: 10.1016/0968-0004(94)90133-3. [DOI] [PubMed] [Google Scholar]
  47. David M., Petricoin E., 3rd, Benjamin C., Pine R., Weber M. J., Larner A. C. Requirement for MAP kinase (ERK2) activity in interferon alpha- and interferon beta-stimulated gene expression through STAT proteins. Science. 1995 Sep 22;269(5231):1721–1723. doi: 10.1126/science.7569900. [DOI] [PubMed] [Google Scholar]
  48. DeVivo M., Iyengar R. G protein pathways: signal processing by effectors. Mol Cell Endocrinol. 1994 Apr;100(1-2):65–70. doi: 10.1016/0303-7207(94)90280-1. [DOI] [PubMed] [Google Scholar]
  49. Decker S. J. Nerve growth factor-induced growth arrest and induction of p21Cip1/WAF1 in NIH-3T3 cells expressing TrkA. J Biol Chem. 1995 Dec 29;270(52):30841–30844. doi: 10.1074/jbc.270.52.30841. [DOI] [PubMed] [Google Scholar]
  50. Decker S. J. Transmembrane signaling by epidermal growth factor receptors lacking autophosphorylation sites. J Biol Chem. 1993 May 5;268(13):9176–9179. [PubMed] [Google Scholar]
  51. Dent P., Jelinek T., Morrison D. K., Weber M. J., Sturgill T. W. Reversal of Raf-1 activation by purified and membrane-associated protein phosphatases. Science. 1995 Jun 30;268(5219):1902–1906. doi: 10.1126/science.7604263. [DOI] [PubMed] [Google Scholar]
  52. Divecha N., Irvine R. F. Phospholipid signaling. Cell. 1995 Jan 27;80(2):269–278. doi: 10.1016/0092-8674(95)90409-3. [DOI] [PubMed] [Google Scholar]
  53. Dong Chen, Waters S. B., Holt K. H., Pessin J. E. SOS phosphorylation and disassociation of the Grb2-SOS complex by the ERK and JNK signaling pathways. J Biol Chem. 1996 Mar 15;271(11):6328–6332. doi: 10.1074/jbc.271.11.6328. [DOI] [PubMed] [Google Scholar]
  54. Dorow D. S., Devereux L., Tu G. F., Price G., Nicholl J. K., Sutherland G. R., Simpson R. J. Complete nucleotide sequence, expression, and chromosomal localisation of human mixed-lineage kinase 2. Eur J Biochem. 1995 Dec 1;234(2):492–500. doi: 10.1111/j.1432-1033.1995.492_b.x. [DOI] [PubMed] [Google Scholar]
  55. Downward J. The GRB2/Sem-5 adaptor protein. FEBS Lett. 1994 Jan 31;338(2):113–117. doi: 10.1016/0014-5793(94)80346-3. [DOI] [PubMed] [Google Scholar]
  56. Drugan J. K., Khosravi-Far R., White M. A., Der C. J., Sung Y. J., Hwang Y. W., Campbell S. L. Ras interaction with two distinct binding domains in Raf-1 may be required for Ras transformation. J Biol Chem. 1996 Jan 5;271(1):233–237. doi: 10.1074/jbc.271.1.233. [DOI] [PubMed] [Google Scholar]
  57. Dérijard B., Hibi M., Wu I. H., Barrett T., Su B., Deng T., Karin M., Davis R. J. JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell. 1994 Mar 25;76(6):1025–1037. doi: 10.1016/0092-8674(94)90380-8. [DOI] [PubMed] [Google Scholar]
  58. Dérijard B., Raingeaud J., Barrett T., Wu I. H., Han J., Ulevitch R. J., Davis R. J. Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms. Science. 1995 Feb 3;267(5198):682–685. doi: 10.1126/science.7839144. [DOI] [PubMed] [Google Scholar]
  59. Eldar-Finkelman H., Seger R., Vandenheede J. R., Krebs E. G. Inactivation of glycogen synthase kinase-3 by epidermal growth factor is mediated by mitogen-activated protein kinase/p90 ribosomal protein S6 kinase signaling pathway in NIH/3T3 cells. J Biol Chem. 1995 Jan 20;270(3):987–990. doi: 10.1074/jbc.270.3.987. [DOI] [PubMed] [Google Scholar]
  60. Elion E. A. Ste5: a meeting place for MAP kinases and their associates. Trends Cell Biol. 1995 Aug;5(8):322–327. doi: 10.1016/s0962-8924(00)89055-8. [DOI] [PubMed] [Google Scholar]
  61. English J. M., Vanderbilt C. A., Xu S., Marcus S., Cobb M. H. Isolation of MEK5 and differential expression of alternatively spliced forms. J Biol Chem. 1995 Dec 1;270(48):28897–28902. doi: 10.1074/jbc.270.48.28897. [DOI] [PubMed] [Google Scholar]
  62. Erhardt P., Troppmair J., Rapp U. R., Cooper G. M. Differential regulation of Raf-1 and B-Raf and Ras-dependent activation of mitogen-activated protein kinase by cyclic AMP in PC12 cells. Mol Cell Biol. 1995 Oct;15(10):5524–5530. doi: 10.1128/mcb.15.10.5524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Erpel T., Courtneidge S. A. Src family protein tyrosine kinases and cellular signal transduction pathways. Curr Opin Cell Biol. 1995 Apr;7(2):176–182. doi: 10.1016/0955-0674(95)80025-5. [DOI] [PubMed] [Google Scholar]
  64. Faure M., Voyno-Yasenetskaya T. A., Bourne H. R. cAMP and beta gamma subunits of heterotrimeric G proteins stimulate the mitogen-activated protein kinase pathway in COS-7 cells. J Biol Chem. 1994 Mar 18;269(11):7851–7854. [PubMed] [Google Scholar]
  65. Feng S., Chen J. K., Yu H., Simon J. A., Schreiber S. L. Two binding orientations for peptides to the Src SH3 domain: development of a general model for SH3-ligand interactions. Science. 1994 Nov 18;266(5188):1241–1247. doi: 10.1126/science.7526465. [DOI] [PubMed] [Google Scholar]
  66. Fialkow L., Chan C. K., Rotin D., Grinstein S., Downey G. P. Activation of the mitogen-activated protein kinase signaling pathway in neutrophils. Role of oxidants. J Biol Chem. 1994 Dec 9;269(49):31234–31242. [PubMed] [Google Scholar]
  67. Fiol C. J., Williams J. S., Chou C. H., Wang Q. M., Roach P. J., Andrisani O. M. A secondary phosphorylation of CREB341 at Ser129 is required for the cAMP-mediated control of gene expression. A role for glycogen synthase kinase-3 in the control of gene expression. J Biol Chem. 1994 Dec 23;269(51):32187–32193. [PubMed] [Google Scholar]
  68. Franke T. F., Yang S. I., Chan T. O., Datta K., Kazlauskas A., Morrison D. K., Kaplan D. R., Tsichlis P. N. The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell. 1995 Jun 2;81(5):727–736. doi: 10.1016/0092-8674(95)90534-0. [DOI] [PubMed] [Google Scholar]
  69. Franklin C. C., Kraft A. S. Constitutively active MAP kinase kinase (MEK1) stimulates SAP kinase and c-Jun transcriptional activity in U937 human leukemic cells. Oncogene. 1995 Dec 7;11(11):2365–2374. [PubMed] [Google Scholar]
  70. Franklin R. A., Tordai A., Patel H., Gardner A. M., Johnson G. L., Gelfand E. W. Ligation of the T cell receptor complex results in activation of the Ras/Raf-1/MEK/MAPK cascade in human T lymphocytes. J Clin Invest. 1994 May;93(5):2134–2140. doi: 10.1172/JCI117209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Freshney N. W., Rawlinson L., Guesdon F., Jones E., Cowley S., Hsuan J., Saklatvala J. Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of Hsp27. Cell. 1994 Sep 23;78(6):1039–1049. doi: 10.1016/0092-8674(94)90278-x. [DOI] [PubMed] [Google Scholar]
  72. Galaktionov K., Jessus C., Beach D. Raf1 interaction with Cdc25 phosphatase ties mitogenic signal transduction to cell cycle activation. Genes Dev. 1995 May 1;9(9):1046–1058. doi: 10.1101/gad.9.9.1046. [DOI] [PubMed] [Google Scholar]
  73. Galaktionov K., Lee A. K., Eckstein J., Draetta G., Meckler J., Loda M., Beach D. CDC25 phosphatases as potential human oncogenes. Science. 1995 Sep 15;269(5230):1575–1577. doi: 10.1126/science.7667636. [DOI] [PubMed] [Google Scholar]
  74. Ginty D. D., Bonni A., Greenberg M. E. Nerve growth factor activates a Ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB. Cell. 1994 Jun 3;77(5):713–725. doi: 10.1016/0092-8674(94)90055-8. [DOI] [PubMed] [Google Scholar]
  75. Gotoh N., Tojo A., Muroya K., Hashimoto Y., Hattori S., Nakamura S., Takenawa T., Yazaki Y., Shibuya M. Epidermal growth factor-receptor mutant lacking the autophosphorylation sites induces phosphorylation of Shc protein and Shc-Grb2/ASH association and retains mitogenic activity. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):167–171. doi: 10.1073/pnas.91.1.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Gutmann D. H., Geist R. T., Wright D. E., Snider W. D. Expression of the neurofibromatosis 1 (NF1) isoforms in developing and adult rat tissues. Cell Growth Differ. 1995 Mar;6(3):315–323. [PubMed] [Google Scholar]
  77. Han J., Lee J. D., Bibbs L., Ulevitch R. J. A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science. 1994 Aug 5;265(5173):808–811. doi: 10.1126/science.7914033. [DOI] [PubMed] [Google Scholar]
  78. Han J., Lee J. D., Jiang Y., Li Z., Feng L., Ulevitch R. J. Characterization of the structure and function of a novel MAP kinase kinase (MKK6). J Biol Chem. 1996 Feb 9;271(6):2886–2891. doi: 10.1074/jbc.271.6.2886. [DOI] [PubMed] [Google Scholar]
  79. Harlan J. E., Hajduk P. J., Yoon H. S., Fesik S. W. Pleckstrin homology domains bind to phosphatidylinositol-4,5-bisphosphate. Nature. 1994 Sep 8;371(6493):168–170. doi: 10.1038/371168a0. [DOI] [PubMed] [Google Scholar]
  80. He X., Saint-Jeannet J. P., Woodgett J. R., Varmus H. E., Dawid I. B. Glycogen synthase kinase-3 and dorsoventral patterning in Xenopus embryos. Nature. 1995 Apr 13;374(6523):617–622. doi: 10.1038/374617a0. [DOI] [PubMed] [Google Scholar]
  81. Heidenreich K. A., Kummer J. L. Inhibition of p38 mitogen-activated protein kinase by insulin in cultured fetal neurons. J Biol Chem. 1996 Apr 26;271(17):9891–9894. doi: 10.1074/jbc.271.17.9891. [DOI] [PubMed] [Google Scholar]
  82. Heldin C. H. Dimerization of cell surface receptors in signal transduction. Cell. 1995 Jan 27;80(2):213–223. doi: 10.1016/0092-8674(95)90404-2. [DOI] [PubMed] [Google Scholar]
  83. Henkemeyer M., Rossi D. J., Holmyard D. P., Puri M. C., Mbamalu G., Harpal K., Shih T. S., Jacks T., Pawson T. Vascular system defects and neuronal apoptosis in mice lacking ras GTPase-activating protein. Nature. 1995 Oct 26;377(6551):695–701. doi: 10.1038/377695a0. [DOI] [PubMed] [Google Scholar]
  84. Hill C. S., Treisman R. Differential activation of c-fos promoter elements by serum, lysophosphatidic acid, G proteins and polypeptide growth factors. EMBO J. 1995 Oct 16;14(20):5037–5047. doi: 10.1002/j.1460-2075.1995.tb00186.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Hirai S., Izawa M., Osada S., Spyrou G., Ohno S. Activation of the JNK pathway by distantly related protein kinases, MEKK and MUK. Oncogene. 1996 Feb 1;12(3):641–650. [PubMed] [Google Scholar]
  86. Horii Y., Beeler J. F., Sakaguchi K., Tachibana M., Miki T. A novel oncogene, ost, encodes a guanine nucleotide exchange factor that potentially links Rho and Rac signaling pathways. EMBO J. 1994 Oct 17;13(20):4776–4786. doi: 10.1002/j.1460-2075.1994.tb06803.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Hu C. D., Kariya K., Tamada M., Akasaka K., Shirouzu M., Yokoyama S., Kataoka T. Cysteine-rich region of Raf-1 interacts with activator domain of post-translationally modified Ha-Ras. J Biol Chem. 1995 Dec 22;270(51):30274–30277. doi: 10.1074/jbc.270.51.30274. [DOI] [PubMed] [Google Scholar]
  88. Hu Q., Milfay D., Williams L. T. Binding of NCK to SOS and activation of ras-dependent gene expression. Mol Cell Biol. 1995 Mar;15(3):1169–1174. doi: 10.1128/mcb.15.3.1169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Huby R. D., Carlile G. W., Ley S. C. Interactions between the protein-tyrosine kinase ZAP-70, the proto-oncoprotein Vav, and tubulin in Jurkat T cells. J Biol Chem. 1995 Dec 22;270(51):30241–30244. doi: 10.1074/jbc.270.51.30241. [DOI] [PubMed] [Google Scholar]
  90. Hunter T. Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell. 1995 Jan 27;80(2):225–236. doi: 10.1016/0092-8674(95)90405-0. [DOI] [PubMed] [Google Scholar]
  91. Hunter T. When is a lipid kinase not a lipid kinase? When it is a protein kinase. Cell. 1995 Oct 6;83(1):1–4. doi: 10.1016/0092-8674(95)90225-2. [DOI] [PubMed] [Google Scholar]
  92. Hyvönen M., Macias M. J., Nilges M., Oschkinat H., Saraste M., Wilmanns M. Structure of the binding site for inositol phosphates in a PH domain. EMBO J. 1995 Oct 2;14(19):4676–4685. doi: 10.1002/j.1460-2075.1995.tb00149.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  93. Häfner S., Adler H. S., Mischak H., Janosch P., Heidecker G., Wolfman A., Pippig S., Lohse M., Ueffing M., Kolch W. Mechanism of inhibition of Raf-1 by protein kinase A. Mol Cell Biol. 1994 Oct;14(10):6696–6703. doi: 10.1128/mcb.14.10.6696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. Ihle J. N. Cytokine receptor signalling. Nature. 1995 Oct 19;377(6550):591–594. doi: 10.1038/377591a0. [DOI] [PubMed] [Google Scholar]
  95. Inglese J., Koch W. J., Touhara K., Lefkowitz R. J. G beta gamma interactions with PH domains and Ras-MAPK signaling pathways. Trends Biochem Sci. 1995 Apr;20(4):151–156. doi: 10.1016/s0968-0004(00)88992-6. [DOI] [PubMed] [Google Scholar]
  96. Jaiswal R. K., Moodie S. A., Wolfman A., Landreth G. E. The mitogen-activated protein kinase cascade is activated by B-Raf in response to nerve growth factor through interaction with p21ras. Mol Cell Biol. 1994 Oct;14(10):6944–6953. doi: 10.1128/mcb.14.10.6944. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. Jakobi R., Chen C. J., Tuazon P. T., Traugh J. A. Molecular cloning and sequencing of the cytostatic G protein-activated protein kinase PAK I. J Biol Chem. 1996 Mar 15;271(11):6206–6211. doi: 10.1074/jbc.271.11.6206. [DOI] [PubMed] [Google Scholar]
  98. Jamal S., Ziff E. B. Raf phosphorylates p53 in vitro and potentiates p53-dependent transcriptional transactivation in vivo. Oncogene. 1995 Jun 1;10(11):2095–2101. [PubMed] [Google Scholar]
  99. Jelinek T., Catling A. D., Reuter C. W., Moodie S. A., Wolfman A., Weber M. J. RAS and RAF-1 form a signalling complex with MEK-1 but not MEK-2. Mol Cell Biol. 1994 Dec;14(12):8212–8218. doi: 10.1128/mcb.14.12.8212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  100. Jelinek T., Dent P., Sturgill T. W., Weber M. J. Ras-induced activation of Raf-1 is dependent on tyrosine phosphorylation. Mol Cell Biol. 1996 Mar;16(3):1027–1034. doi: 10.1128/mcb.16.3.1027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  101. Jiang H., Luo J. Q., Urano T., Frankel P., Lu Z., Foster D. A., Feig L. A. Involvement of Ral GTPase in v-Src-induced phospholipase D activation. Nature. 1995 Nov 23;378(6555):409–412. doi: 10.1038/378409a0. [DOI] [PubMed] [Google Scholar]
  102. Johnson L. N., Noble M. E., Owen D. J. Active and inactive protein kinases: structural basis for regulation. Cell. 1996 Apr 19;85(2):149–158. doi: 10.1016/s0092-8674(00)81092-2. [DOI] [PubMed] [Google Scholar]
  103. Johnson M. R., DeClue J. E., Felzmann S., Vass W. C., Xu G., White R., Lowy D. R. Neurofibromin can inhibit Ras-dependent growth by a mechanism independent of its GTPase-accelerating function. Mol Cell Biol. 1994 Jan;14(1):641–645. doi: 10.1128/mcb.14.1.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. Joneson T., White M. A., Wigler M. H., Bar-Sagi D. Stimulation of membrane ruffling and MAP kinase activation by distinct effectors of RAS. Science. 1996 Feb 9;271(5250):810–812. doi: 10.1126/science.271.5250.810. [DOI] [PubMed] [Google Scholar]
  105. Kavanaugh W. M., Williams L. T. An alternative to SH2 domains for binding tyrosine-phosphorylated proteins. Science. 1994 Dec 16;266(5192):1862–1865. doi: 10.1126/science.7527937. [DOI] [PubMed] [Google Scholar]
  106. Keyse S. M. An emerging family of dual specificity MAP kinase phosphatases. Biochim Biophys Acta. 1995 Mar 16;1265(2-3):152–160. doi: 10.1016/0167-4889(94)00211-v. [DOI] [PubMed] [Google Scholar]
  107. Kharbanda S., Pandey P., Ren R., Mayer B., Zon L., Kufe D. c-Abl activation regulates induction of the SEK1/stress-activated protein kinase pathway in the cellular response to 1-beta-D-arabinofuranosylcytosine. J Biol Chem. 1995 Dec 22;270(51):30278–30281. doi: 10.1074/jbc.270.51.30278. [DOI] [PubMed] [Google Scholar]
  108. Khosravi-Far R., Der C. J. The Ras signal transduction pathway. Cancer Metastasis Rev. 1994 Mar;13(1):67–89. doi: 10.1007/BF00690419. [DOI] [PubMed] [Google Scholar]
  109. Khosravi-Far R., Solski P. A., Clark G. J., Kinch M. S., Der C. J. Activation of Rac1, RhoA, and mitogen-activated protein kinases is required for Ras transformation. Mol Cell Biol. 1995 Nov;15(11):6443–6453. doi: 10.1128/mcb.15.11.6443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  110. Klint P., Kanda S., Claesson-Welsh L. Shc and a novel 89-kDa component couple to the Grb2-Sos complex in fibroblast growth factor-2-stimulated cells. J Biol Chem. 1995 Oct 6;270(40):23337–23344. doi: 10.1074/jbc.270.40.23337. [DOI] [PubMed] [Google Scholar]
  111. Knaus U. G., Morris S., Dong H. J., Chernoff J., Bokoch G. M. Regulation of human leukocyte p21-activated kinases through G protein--coupled receptors. Science. 1995 Jul 14;269(5221):221–223. doi: 10.1126/science.7618083. [DOI] [PubMed] [Google Scholar]
  112. Kozma R., Ahmed S., Best A., Lim L. The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodia in Swiss 3T3 fibroblasts. Mol Cell Biol. 1995 Apr;15(4):1942–1952. doi: 10.1128/mcb.15.4.1942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  113. Kumar S., McLaughlin M. M., McDonnell P. C., Lee J. C., Livi G. P., Young P. R. Human mitogen-activated protein kinase CSBP1, but not CSBP2, complements a hog1 deletion in yeast. J Biol Chem. 1995 Dec 8;270(49):29043–29046. doi: 10.1074/jbc.270.49.29043. [DOI] [PubMed] [Google Scholar]
  114. Ladbury J. E., Lemmon M. A., Zhou M., Green J., Botfield M. C., Schlessinger J. Measurement of the binding of tyrosyl phosphopeptides to SH2 domains: a reappraisal. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3199–3203. doi: 10.1073/pnas.92.8.3199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  115. Lander H. M., Ogiste J. S., Teng K. K., Novogrodsky A. p21ras as a common signaling target of reactive free radicals and cellular redox stress. J Biol Chem. 1995 Sep 8;270(36):21195–21198. doi: 10.1074/jbc.270.36.21195. [DOI] [PubMed] [Google Scholar]
  116. Lange-Carter C. A., Johnson G. L. Ras-dependent growth factor regulation of MEK kinase in PC12 cells. Science. 1994 Sep 2;265(5177):1458–1461. doi: 10.1126/science.8073291. [DOI] [PubMed] [Google Scholar]
  117. Lavoie J. N., Lambert H., Hickey E., Weber L. A., Landry J. Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27. Mol Cell Biol. 1995 Jan;15(1):505–516. doi: 10.1128/mcb.15.1.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  118. Lee S. B., Rhee S. G. Significance of PIP2 hydrolysis and regulation of phospholipase C isozymes. Curr Opin Cell Biol. 1995 Apr;7(2):183–189. doi: 10.1016/0955-0674(95)80026-3. [DOI] [PubMed] [Google Scholar]
  119. Leevers S. J., Paterson H. F., Marshall C. J. Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane. Nature. 1994 Jun 2;369(6479):411–414. doi: 10.1038/369411a0. [DOI] [PubMed] [Google Scholar]
  120. Lemmon M. A., Ferguson K. M., O'Brien R., Sigler P. B., Schlessinger J. Specific and high-affinity binding of inositol phosphates to an isolated pleckstrin homology domain. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10472–10476. doi: 10.1073/pnas.92.23.10472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  121. Li S., Janosch P., Tanji M., Rosenfeld G. C., Waymire J. C., Mischak H., Kolch W., Sedivy J. M. Regulation of Raf-1 kinase activity by the 14-3-3 family of proteins. EMBO J. 1995 Feb 15;14(4):685–696. doi: 10.1002/j.1460-2075.1995.tb07047.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  122. Li S., Janosch P., Tanji M., Rosenfeld G. C., Waymire J. C., Mischak H., Kolch W., Sedivy J. M. Regulation of Raf-1 kinase activity by the 14-3-3 family of proteins. EMBO J. 1995 Feb 15;14(4):685–696. doi: 10.1002/j.1460-2075.1995.tb07047.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  123. Li S., Sedivy J. M. Raf-1 protein kinase activates the NF-kappa B transcription factor by dissociating the cytoplasmic NF-kappa B-I kappa B complex. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9247–9251. doi: 10.1073/pnas.90.20.9247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  124. Lin A., Minden A., Martinetto H., Claret F. X., Lange-Carter C., Mercurio F., Johnson G. L., Karin M. Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2. Science. 1995 Apr 14;268(5208):286–290. doi: 10.1126/science.7716521. [DOI] [PubMed] [Google Scholar]
  125. Liu J. P. Protein kinase C and its substrates. Mol Cell Endocrinol. 1996 Jan 15;116(1):1–29. doi: 10.1016/0303-7207(95)03706-3. [DOI] [PubMed] [Google Scholar]
  126. Lowe P. N., Skinner R. H. Regulation of Ras signal transduction in normal and transformed cells. Cell Signal. 1994 Feb;6(2):109–123. doi: 10.1016/0898-6568(94)90067-1. [DOI] [PubMed] [Google Scholar]
  127. Lowy D. R., Willumsen B. M. Function and regulation of ras. Annu Rev Biochem. 1993;62:851–891. doi: 10.1146/annurev.bi.62.070193.004223. [DOI] [PubMed] [Google Scholar]
  128. Luttrell L. M., van Biesen T., Hawes B. E., Koch W. J., Touhara K., Lefkowitz R. J. G beta gamma subunits mediate mitogen-activated protein kinase activation by the tyrosine kinase insulin-like growth factor 1 receptor. J Biol Chem. 1995 Jul 14;270(28):16495–16498. doi: 10.1074/jbc.270.28.16495. [DOI] [PubMed] [Google Scholar]
  129. Maekawa M., Li S., Iwamatsu A., Morishita T., Yokota K., Imai Y., Kohsaka S., Nakamura S., Hattori S. A novel mammalian Ras GTPase-activating protein which has phospholipid-binding and Btk homology regions. Mol Cell Biol. 1994 Oct;14(10):6879–6885. doi: 10.1128/mcb.14.10.6879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  130. Maher J., Baker D. A., Manning M., Dibb N. J., Roberts I. A. Evidence for cell-specific differences in transformation by N-, H- and K-ras. Oncogene. 1995 Oct 19;11(8):1639–1647. [PubMed] [Google Scholar]
  131. Malarkey K., Belham C. M., Paul A., Graham A., McLees A., Scott P. H., Plevin R. The regulation of tyrosine kinase signalling pathways by growth factor and G-protein-coupled receptors. Biochem J. 1995 Jul 15;309(Pt 2):361–375. doi: 10.1042/bj3090361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  132. Manser E., Leung T., Salihuddin H., Zhao Z. S., Lim L. A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature. 1994 Jan 6;367(6458):40–46. doi: 10.1038/367040a0. [DOI] [PubMed] [Google Scholar]
  133. Mansour S. J., Candia J. M., Gloor K. K., Ahn N. G. Constitutively active mitogen-activated protein kinase kinase 1 (MAPKK1) and MAPKK2 mediate similar transcriptional and morphological responses. Cell Growth Differ. 1996 Feb;7(2):243–250. [PubMed] [Google Scholar]
  134. Mansour S. J., Matten W. T., Hermann A. S., Candia J. M., Rong S., Fukasawa K., Vande Woude G. F., Ahn N. G. Transformation of mammalian cells by constitutively active MAP kinase kinase. Science. 1994 Aug 12;265(5174):966–970. doi: 10.1126/science.8052857. [DOI] [PubMed] [Google Scholar]
  135. Marais R., Light Y., Paterson H. F., Marshall C. J. Ras recruits Raf-1 to the plasma membrane for activation by tyrosine phosphorylation. EMBO J. 1995 Jul 3;14(13):3136–3145. doi: 10.1002/j.1460-2075.1995.tb07316.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  136. Marshall C. J. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell. 1995 Jan 27;80(2):179–185. doi: 10.1016/0092-8674(95)90401-8. [DOI] [PubMed] [Google Scholar]
  137. Marshall M. S. Ras target proteins in eukaryotic cells. FASEB J. 1995 Oct;9(13):1311–1318. doi: 10.1096/fasebj.9.13.7557021. [DOI] [PubMed] [Google Scholar]
  138. Matsuda S., Kawasaki H., Moriguchi T., Gotoh Y., Nishida E. Activation of protein kinase cascades by osmotic shock. J Biol Chem. 1995 May 26;270(21):12781–12786. doi: 10.1074/jbc.270.21.12781. [DOI] [PubMed] [Google Scholar]
  139. McCarthy S. A., Samuels M. L., Pritchard C. A., Abraham J. A., McMahon M. Rapid induction of heparin-binding epidermal growth factor/diphtheria toxin receptor expression by Raf and Ras oncogenes. Genes Dev. 1995 Aug 15;9(16):1953–1964. doi: 10.1101/gad.9.16.1953. [DOI] [PubMed] [Google Scholar]
  140. McGlade J., Brunkhorst B., Anderson D., Mbamalu G., Settleman J., Dedhar S., Rozakis-Adcock M., Chen L. B., Pawson T. The N-terminal region of GAP regulates cytoskeletal structure and cell adhesion. EMBO J. 1993 Aug;12(8):3073–3081. doi: 10.1002/j.1460-2075.1993.tb05976.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  141. McLaughlin M. M., Kumar S., McDonnell P. C., Van Horn S., Lee J. C., Livi G. P., Young P. R. Identification of mitogen-activated protein (MAP) kinase-activated protein kinase-3, a novel substrate of CSBP p38 MAP kinase. J Biol Chem. 1996 Apr 5;271(14):8488–8492. doi: 10.1074/jbc.271.14.8488. [DOI] [PubMed] [Google Scholar]
  142. Michaud N. R., Fabian J. R., Mathes K. D., Morrison D. K. 14-3-3 is not essential for Raf-1 function: identification of Raf-1 proteins that are biologically activated in a 14-3-3- and Ras-independent manner. Mol Cell Biol. 1995 Jun;15(6):3390–3397. doi: 10.1128/mcb.15.6.3390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  143. Milarski K. L., Saltiel A. R. Expression of catalytically inactive Syp phosphatase in 3T3 cells blocks stimulation of mitogen-activated protein kinase by insulin. J Biol Chem. 1994 Aug 19;269(33):21239–21243. [PubMed] [Google Scholar]
  144. Minden A., Lin A., Claret F. X., Abo A., Karin M. Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs. Cell. 1995 Jun 30;81(7):1147–1157. doi: 10.1016/s0092-8674(05)80019-4. [DOI] [PubMed] [Google Scholar]
  145. Minden A., Lin A., McMahon M., Lange-Carter C., Dérijard B., Davis R. J., Johnson G. L., Karin M. Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK. Science. 1994 Dec 9;266(5191):1719–1723. doi: 10.1126/science.7992057. [DOI] [PubMed] [Google Scholar]
  146. Montgomery R. B., Moscatello D. K., Wong A. J., Cooper J. A., Stahl W. L. Differential modulation of mitogen-activated protein (MAP) kinase/extracellular signal-related kinase kinase and MAP kinase activities by a mutant epidermal growth factor receptor. J Biol Chem. 1995 Dec 22;270(51):30562–30566. doi: 10.1074/jbc.270.51.30562. [DOI] [PubMed] [Google Scholar]
  147. Morrison D. K., Heidecker G., Rapp U. R., Copeland T. D. Identification of the major phosphorylation sites of the Raf-1 kinase. J Biol Chem. 1993 Aug 15;268(23):17309–17316. [PubMed] [Google Scholar]
  148. Musacchio A., Gibson T., Rice P., Thompson J., Saraste M. The PH domain: a common piece in the structural patchwork of signalling proteins. Trends Biochem Sci. 1993 Sep;18(9):343–348. doi: 10.1016/0968-0004(93)90071-t. [DOI] [PubMed] [Google Scholar]
  149. Muslin A. J., Tanner J. W., Allen P. M., Shaw A. S. Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine. Cell. 1996 Mar 22;84(6):889–897. doi: 10.1016/s0092-8674(00)81067-3. [DOI] [PubMed] [Google Scholar]
  150. Nakanishi H., Brewer K. A., Exton J. H. Activation of the zeta isozyme of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem. 1993 Jan 5;268(1):13–16. [PubMed] [Google Scholar]
  151. Newton A. C. Protein kinase C: structure, function, and regulation. J Biol Chem. 1995 Dec 1;270(48):28495–28498. doi: 10.1074/jbc.270.48.28495. [DOI] [PubMed] [Google Scholar]
  152. Nobes C. D., Hall A. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell. 1995 Apr 7;81(1):53–62. doi: 10.1016/0092-8674(95)90370-4. [DOI] [PubMed] [Google Scholar]
  153. Nomanbhoy T. K., Cerione R. Characterization of the interaction between RhoGDI and Cdc42Hs using fluorescence spectroscopy. J Biol Chem. 1996 Apr 26;271(17):10004–10009. doi: 10.1074/jbc.271.17.10004. [DOI] [PubMed] [Google Scholar]
  154. Nuoffer C., Balch W. E. GTPases: multifunctional molecular switches regulating vesicular traffic. Annu Rev Biochem. 1994;63:949–990. doi: 10.1146/annurev.bi.63.070194.004505. [DOI] [PubMed] [Google Scholar]
  155. Park S. H., Weinberg R. A. A putative effector of Ral has homology to Rho/Rac GTPase activating proteins. Oncogene. 1995 Dec 7;11(11):2349–2355. [PubMed] [Google Scholar]
  156. Pawson T. Protein modules and signalling networks. Nature. 1995 Feb 16;373(6515):573–580. doi: 10.1038/373573a0. [DOI] [PubMed] [Google Scholar]
  157. Peng Z. Y., Cartwright C. A. Regulation of the Src tyrosine kinase and Syp tyrosine phosphatase by their cellular association. Oncogene. 1995 Nov 16;11(10):1955–1962. [PubMed] [Google Scholar]
  158. Polakis P., McCormick F. Structural requirements for the interaction of p21ras with GAP, exchange factors, and its biological effector target. J Biol Chem. 1993 May 5;268(13):9157–9160. [PubMed] [Google Scholar]
  159. Prigent S. A., Pillay T. S., Ravichandran K. S., Gullick W. J. Binding of Shc to the NPXY motif is mediated by its N-terminal domain. J Biol Chem. 1995 Sep 22;270(38):22097–22100. doi: 10.1074/jbc.270.38.22097. [DOI] [PubMed] [Google Scholar]
  160. Pritchard C. A., Samuels M. L., Bosch E., McMahon M. Conditionally oncogenic forms of the A-Raf and B-Raf protein kinases display different biological and biochemical properties in NIH 3T3 cells. Mol Cell Biol. 1995 Nov;15(11):6430–6442. doi: 10.1128/mcb.15.11.6430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  161. Qiu R. G., Chen J., Kirn D., McCormick F., Symons M. An essential role for Rac in Ras transformation. Nature. 1995 Mar 30;374(6521):457–459. doi: 10.1038/374457a0. [DOI] [PubMed] [Google Scholar]
  162. Qiu R. G., Chen J., McCormick F., Symons M. A role for Rho in Ras transformation. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11781–11785. doi: 10.1073/pnas.92.25.11781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  163. Quilliam L. A., Khosravi-Far R., Huff S. Y., Der C. J. Guanine nucleotide exchange factors: activators of the Ras superfamily of proteins. Bioessays. 1995 May;17(5):395–404. doi: 10.1002/bies.950170507. [DOI] [PubMed] [Google Scholar]
  164. Raingeaud J., Gupta S., Rogers J. S., Dickens M., Han J., Ulevitch R. J., Davis R. J. Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J Biol Chem. 1995 Mar 31;270(13):7420–7426. doi: 10.1074/jbc.270.13.7420. [DOI] [PubMed] [Google Scholar]
  165. Raingeaud J., Whitmarsh A. J., Barrett T., Dérijard B., Davis R. J. MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway. Mol Cell Biol. 1996 Mar;16(3):1247–1255. doi: 10.1128/mcb.16.3.1247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  166. Rameh L. E., Chen C. S., Cantley L. C. Phosphatidylinositol (3,4,5)P3 interacts with SH2 domains and modulates PI 3-kinase association with tyrosine-phosphorylated proteins. Cell. 1995 Dec 1;83(5):821–830. doi: 10.1016/0092-8674(95)90195-7. [DOI] [PubMed] [Google Scholar]
  167. Reuter C. W., Catling A. D., Jelinek T., Weber M. J. Biochemical analysis of MEK activation in NIH3T3 fibroblasts. Identification of B-Raf and other activators. J Biol Chem. 1995 Mar 31;270(13):7644–7655. doi: 10.1074/jbc.270.13.7644. [DOI] [PubMed] [Google Scholar]
  168. Ridley A. J. Rho-related proteins: actin cytoskeleton and cell cycle. Curr Opin Genet Dev. 1995 Feb;5(1):24–30. doi: 10.1016/s0959-437x(95)90049-7. [DOI] [PubMed] [Google Scholar]
  169. Romero F., Dargemont C., Pozo F., Reeves W. H., Camonis J., Gisselbrecht S., Fischer S. p95vav associates with the nuclear protein Ku-70. Mol Cell Biol. 1996 Jan;16(1):37–44. doi: 10.1128/mcb.16.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  170. Rommel C., Radziwill G., Lovrić J., Noeldeke J., Heinicke T., Jones D., Aitken A., Moelling K. Activated Ras displaces 14-3-3 protein from the amino terminus of c-Raf-1. Oncogene. 1996 Feb 1;12(3):609–619. [PubMed] [Google Scholar]
  171. Rothman J. E. Mechanisms of intracellular protein transport. Nature. 1994 Nov 3;372(6501):55–63. doi: 10.1038/372055a0. [DOI] [PubMed] [Google Scholar]
  172. Rouse J., Cohen P., Trigon S., Morange M., Alonso-Llamazares A., Zamanillo D., Hunt T., Nebreda A. R. A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins. Cell. 1994 Sep 23;78(6):1027–1037. doi: 10.1016/0092-8674(94)90277-1. [DOI] [PubMed] [Google Scholar]
  173. Rozakis-Adcock M., van der Geer P., Mbamalu G., Pawson T. MAP kinase phosphorylation of mSos1 promotes dissociation of mSos1-Shc and mSos1-EGF receptor complexes. Oncogene. 1995 Oct 5;11(7):1417–1426. [PubMed] [Google Scholar]
  174. Russell M., Lange-Carter C. A., Johnson G. L. Direct interaction between Ras and the kinase domain of mitogen-activated protein kinase kinase kinase (MEKK1). J Biol Chem. 1995 May 19;270(20):11757–11760. doi: 10.1074/jbc.270.20.11757. [DOI] [PubMed] [Google Scholar]
  175. Sakata N., Patel H. R., Terada N., Aruffo A., Johnson G. L., Gelfand E. W. Selective activation of c-Jun kinase mitogen-activated protein kinase by CD40 on human B cells. J Biol Chem. 1995 Dec 22;270(51):30823–30828. doi: 10.1074/jbc.270.51.30823. [DOI] [PubMed] [Google Scholar]
  176. Saleem A., Datta R., Yuan Z. M., Kharbanda S., Kufe D. Involvement of stress-activated protein kinase in the cellular response to 1-beta-D-arabinofuranosylcytosine and other DNA-damaging agents. Cell Growth Differ. 1995 Dec;6(12):1651–1658. [PubMed] [Google Scholar]
  177. Salmeron A., Ahmad T. B., Carlile G. W., Pappin D., Narsimhan R. P., Ley S. C. Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase. EMBO J. 1996 Feb 15;15(4):817–826. [PMC free article] [PubMed] [Google Scholar]
  178. Sato K., Sato A., Aoto M., Fukami Y. c-Src phosphorylates epidermal growth factor receptor on tyrosine 845. Biochem Biophys Res Commun. 1995 Oct 24;215(3):1078–1087. doi: 10.1006/bbrc.1995.2574. [DOI] [PubMed] [Google Scholar]
  179. Sawada T., Milarski K. L., Saltiel A. R. Expression of a catalytically inert Syp blocks activation of MAP kinase pathway downstream of p21ras. Biochem Biophys Res Commun. 1995 Sep 14;214(2):737–743. doi: 10.1006/bbrc.1995.2347. [DOI] [PubMed] [Google Scholar]
  180. Schlaepfer D. D., Hanks S. K., Hunter T., van der Geer P. Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase. Nature. 1994 Dec 22;372(6508):786–791. doi: 10.1038/372786a0. [DOI] [PubMed] [Google Scholar]
  181. Schulte T. W., Blagosklonny M. V., Ingui C., Neckers L. Disruption of the Raf-1-Hsp90 molecular complex results in destabilization of Raf-1 and loss of Raf-1-Ras association. J Biol Chem. 1995 Oct 13;270(41):24585–24588. doi: 10.1074/jbc.270.41.24585. [DOI] [PubMed] [Google Scholar]
  182. Seger R., Krebs E. G. The MAPK signaling cascade. FASEB J. 1995 Jun;9(9):726–735. [PubMed] [Google Scholar]
  183. Seger R., Seger D., Reszka A. A., Munar E. S., Eldar-Finkelman H., Dobrowolska G., Jensen A. M., Campbell J. S., Fischer E. H., Krebs E. G. Overexpression of mitogen-activated protein kinase kinase (MAPKK) and its mutants in NIH 3T3 cells. Evidence that MAPKK involvement in cellular proliferation is regulated by phosphorylation of serine residues in its kinase subdomains VII and VIII. J Biol Chem. 1994 Oct 14;269(41):25699–25709. [PubMed] [Google Scholar]
  184. Shirouzu M., Koide H., Fujita-Yoshigaki J., Oshio H., Toyama Y., Yamasaki K., Fuhrman S. A., Villafranca E., Kaziro Y., Yokoyama S. Mutations that abolish the ability of Ha-Ras to associate with Raf-1. Oncogene. 1994 Aug;9(8):2153–2157. [PubMed] [Google Scholar]
  185. Silvennoinen O., Ihle J. N., Schlessinger J., Levy D. E. Interferon-induced nuclear signalling by Jak protein tyrosine kinases. Nature. 1993 Dec 9;366(6455):583–585. doi: 10.1038/366583a0. [DOI] [PubMed] [Google Scholar]
  186. Songyang Z., Cantley L. C. Recognition and specificity in protein tyrosine kinase-mediated signalling. Trends Biochem Sci. 1995 Nov;20(11):470–475. doi: 10.1016/s0968-0004(00)89103-3. [DOI] [PubMed] [Google Scholar]
  187. Songyang Z., Gish G., Mbamalu G., Pawson T., Cantley L. C. A single point mutation switches the specificity of group III Src homology (SH) 2 domains to that of group I SH2 domains. J Biol Chem. 1995 Nov 3;270(44):26029–26032. doi: 10.1074/jbc.270.44.26029. [DOI] [PubMed] [Google Scholar]
  188. Stokoe D., Macdonald S. G., Cadwallader K., Symons M., Hancock J. F. Activation of Raf as a result of recruitment to the plasma membrane. Science. 1994 Jun 3;264(5164):1463–1467. doi: 10.1126/science.7811320. [DOI] [PubMed] [Google Scholar]
  189. Strader C. D., Fong T. M., Graziano M. P., Tota M. R. The family of G-protein-coupled receptors. FASEB J. 1995 Jun;9(9):745–754. [PubMed] [Google Scholar]
  190. Suen K. L., Bustelo X. R., Barbacid M. Lack of evidence for the activation of the Ras/Raf mitogenic pathway by 14-3-3 proteins in mammalian cells. Oncogene. 1995 Sep 7;11(5):825–831. [PubMed] [Google Scholar]
  191. Sun H., Tonks N. K. The coordinated action of protein tyrosine phosphatases and kinases in cell signaling. Trends Biochem Sci. 1994 Nov;19(11):480–485. doi: 10.1016/0968-0004(94)90134-1. [DOI] [PubMed] [Google Scholar]
  192. Sánchez I., Hughes R. T., Mayer B. J., Yee K., Woodgett J. R., Avruch J., Kyriakis J. M., Zon L. I. Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun. Nature. 1994 Dec 22;372(6508):794–798. doi: 10.1038/372794a0. [DOI] [PubMed] [Google Scholar]
  193. Takai Y., Sasaki T., Tanaka K., Nakanishi H. Rho as a regulator of the cytoskeleton. Trends Biochem Sci. 1995 Jun;20(6):227–231. doi: 10.1016/s0968-0004(00)89022-2. [DOI] [PubMed] [Google Scholar]
  194. Terada K., Kaziro Y., Satoh T. Ras is not required for the interleukin 3-induced proliferation of a mouse pro-B cell line, BaF3. J Biol Chem. 1995 Nov 17;270(46):27880–27886. doi: 10.1074/jbc.270.46.27880. [DOI] [PubMed] [Google Scholar]
  195. Therrien M., Chang H. C., Solomon N. M., Karim F. D., Wassarman D. A., Rubin G. M. KSR, a novel protein kinase required for RAS signal transduction. Cell. 1995 Dec 15;83(6):879–888. doi: 10.1016/0092-8674(95)90204-x. [DOI] [PubMed] [Google Scholar]
  196. Touhara K., Hawes B. E., van Biesen T., Lefkowitz R. J. G protein beta gamma subunits stimulate phosphorylation of Shc adapter protein. Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9284–9287. doi: 10.1073/pnas.92.20.9284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  197. Treisman R. Journey to the surface of the cell: Fos regulation and the SRE. EMBO J. 1995 Oct 16;14(20):4905–4913. doi: 10.1002/j.1460-2075.1995.tb00173.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  198. Urano T., Emkey R., Feig L. A. Ral-GTPases mediate a distinct downstream signaling pathway from Ras that facilitates cellular transformation. EMBO J. 1996 Feb 15;15(4):810–816. [PMC free article] [PubMed] [Google Scholar]
  199. Vogel K. S., Brannan C. I., Jenkins N. A., Copeland N. G., Parada L. F. Loss of neurofibromin results in neurotrophin-independent survival of embryonic sensory and sympathetic neurons. Cell. 1995 Sep 8;82(5):733–742. doi: 10.1016/0092-8674(95)90470-0. [DOI] [PubMed] [Google Scholar]
  200. Vojtek A. B., Cooper J. A. Rho family members: activators of MAP kinase cascades. Cell. 1995 Aug 25;82(4):527–529. doi: 10.1016/0092-8674(95)90023-3. [DOI] [PubMed] [Google Scholar]
  201. Wang Q. M., Fiol C. J., DePaoli-Roach A. A., Roach P. J. Glycogen synthase kinase-3 beta is a dual specificity kinase differentially regulated by tyrosine and serine/threonine phosphorylation. J Biol Chem. 1994 May 20;269(20):14566–14574. [PubMed] [Google Scholar]
  202. Wang Q. M., Vik T. A., Ryder J. W., Roach P. J. Phosphorylation and activation of p90rsk by glycogen synthase kinase-3. Biochem Biophys Res Commun. 1995 Mar 17;208(2):796–801. doi: 10.1006/bbrc.1995.1407. [DOI] [PubMed] [Google Scholar]
  203. Waskiewicz A. J., Cooper J. A. Mitogen and stress response pathways: MAP kinase cascades and phosphatase regulation in mammals and yeast. Curr Opin Cell Biol. 1995 Dec;7(6):798–805. doi: 10.1016/0955-0674(95)80063-8. [DOI] [PubMed] [Google Scholar]
  204. Waters S. B., Holt K. H., Ross S. E., Syu L. J., Guan K. L., Saltiel A. R., Koretzky G. A., Pessin J. E. Desensitization of Ras activation by a feedback disassociation of the SOS-Grb2 complex. J Biol Chem. 1995 Sep 8;270(36):20883–20886. doi: 10.1074/jbc.270.36.20883. [DOI] [PubMed] [Google Scholar]
  205. Welsh G. I., Foulstone E. J., Young S. W., Tavaré J. M., Proud C. G. Wortmannin inhibits the effects of insulin and serum on the activities of glycogen synthase kinase-3 and mitogen-activated protein kinase. Biochem J. 1994 Oct 1;303(Pt 1):15–20. doi: 10.1042/bj3030015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  206. Wera S., Hemmings B. A. Serine/threonine protein phosphatases. Biochem J. 1995 Oct 1;311(Pt 1):17–29. doi: 10.1042/bj3110017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  207. Westwick J. K., Bielawska A. E., Dbaibo G., Hannun Y. A., Brenner D. A. Ceramide activates the stress-activated protein kinases. J Biol Chem. 1995 Sep 29;270(39):22689–22692. doi: 10.1074/jbc.270.39.22689. [DOI] [PubMed] [Google Scholar]
  208. Wiesmüller L., Wittinghofer F. Signal transduction pathways involving Ras. Mini review. Cell Signal. 1994 Mar;6(3):247–267. doi: 10.1016/0898-6568(94)90030-2. [DOI] [PubMed] [Google Scholar]
  209. Winston B. W., Remigio L. K., Riches D. W. Preferential involvement of MEK1 in the tumor necrosis factor-alpha-induced activation of p42mapk/erk2 in mouse macrophages. J Biol Chem. 1995 Nov 17;270(46):27391–27394. doi: 10.1074/jbc.270.46.27391. [DOI] [PubMed] [Google Scholar]
  210. Winston L. A., Hunter T. JAK2, Ras, and Raf are required for activation of extracellular signal-regulated kinase/mitogen-activated protein kinase by growth hormone. J Biol Chem. 1995 Dec 29;270(52):30837–30840. doi: 10.1074/jbc.270.52.30837. [DOI] [PubMed] [Google Scholar]
  211. Wu X., Noh S. J., Zhou G., Dixon J. E., Guan K. L. Selective activation of MEK1 but not MEK2 by A-Raf from epidermal growth factor-stimulated Hela cells. J Biol Chem. 1996 Feb 9;271(6):3265–3271. doi: 10.1074/jbc.271.6.3265. [DOI] [PubMed] [Google Scholar]
  212. Xia Z., Dickens M., Raingeaud J., Davis R. J., Greenberg M. E. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science. 1995 Nov 24;270(5240):1326–1331. doi: 10.1126/science.270.5240.1326. [DOI] [PubMed] [Google Scholar]
  213. Xiao S., Rose D. W., Sasaoka T., Maegawa H., Burke T. R., Jr, Roller P. P., Shoelson S. E., Olefsky J. M. Syp (SH-PTP2) is a positive mediator of growth factor-stimulated mitogenic signal transduction. J Biol Chem. 1994 Aug 19;269(33):21244–21248. [PubMed] [Google Scholar]
  214. Xie W., Herschman H. R. v-src induces prostaglandin synthase 2 gene expression by activation of the c-Jun N-terminal kinase and the c-Jun transcription factor. J Biol Chem. 1995 Nov 17;270(46):27622–27628. doi: 10.1074/jbc.270.46.27622. [DOI] [PubMed] [Google Scholar]
  215. Xie Y., Pendergast A. M., Hung M. C. Dominant-negative mutants of Grb2 induced reversal of the transformed phenotypes caused by the point mutation-activated rat HER-2/Neu. J Biol Chem. 1995 Dec 22;270(51):30717–30724. doi: 10.1074/jbc.270.51.30717. [DOI] [PubMed] [Google Scholar]
  216. Xu S., Robbins D., Frost J., Dang A., Lange-Carter C., Cobb M. H. MEKK1 phosphorylates MEK1 and MEK2 but does not cause activation of mitogen-activated protein kinase. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6808–6812. doi: 10.1073/pnas.92.15.6808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  217. Yamaguchi K., Shirakabe K., Shibuya H., Irie K., Oishi I., Ueno N., Taniguchi T., Nishida E., Matsumoto K. Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction. Science. 1995 Dec 22;270(5244):2008–2011. doi: 10.1126/science.270.5244.2008. [DOI] [PubMed] [Google Scholar]
  218. Yan M., Dai T., Deak J. C., Kyriakis J. M., Zon L. I., Woodgett J. R., Templeton D. J. Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1. Nature. 1994 Dec 22;372(6508):798–800. doi: 10.1038/372798a0. [DOI] [PubMed] [Google Scholar]
  219. Yao B., Zhang Y., Delikat S., Mathias S., Basu S., Kolesnick R. Phosphorylation of Raf by ceramide-activated protein kinase. Nature. 1995 Nov 16;378(6554):307–310. doi: 10.1038/378307a0. [DOI] [PubMed] [Google Scholar]
  220. Yao L., Kawakami Y., Kawakami T. The pleckstrin homology domain of Bruton tyrosine kinase interacts with protein kinase C. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):9175–9179. doi: 10.1073/pnas.91.19.9175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  221. Yao R., Cooper G. M. Regulation of the Ras signaling pathway by GTPase-activating protein in PC12 cells. Oncogene. 1995 Oct 19;11(8):1607–1614. [PubMed] [Google Scholar]
  222. Yoder-Hill J., Golubic M., Stacey D. W. A conserved region of c-Ha-Ras is required for efficient GTPase stimulation by GTPase activating protein but not neurofibromin. J Biol Chem. 1995 Nov 17;270(46):27615–27621. doi: 10.1074/jbc.270.46.27615. [DOI] [PubMed] [Google Scholar]
  223. Zhang S., Han J., Sells M. A., Chernoff J., Knaus U. G., Ulevitch R. J., Bokoch G. M. Rho family GTPases regulate p38 mitogen-activated protein kinase through the downstream mediator Pak1. J Biol Chem. 1995 Oct 13;270(41):23934–23936. doi: 10.1074/jbc.270.41.23934. [DOI] [PubMed] [Google Scholar]
  224. Zheng C. F., Guan K. L. Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues. EMBO J. 1994 Mar 1;13(5):1123–1131. doi: 10.1002/j.1460-2075.1994.tb06361.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  225. Zhou M. M., Ravichandran K. S., Olejniczak E. F., Petros A. M., Meadows R. P., Sattler M., Harlan J. E., Wade W. S., Burakoff S. J., Fesik S. W. Structure and ligand recognition of the phosphotyrosine binding domain of Shc. Nature. 1995 Dec 7;378(6557):584–592. doi: 10.1038/378584a0. [DOI] [PubMed] [Google Scholar]
  226. Zhu A. X., Zhao Y., Moller D. E., Flier J. S. Cloning and characterization of p97MAPK, a novel human homolog of rat ERK-3. Mol Cell Biol. 1994 Dec;14(12):8202–8211. doi: 10.1128/mcb.14.12.8202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  227. de Vries-Smits A. M., Pronk G. J., Medema J. P., Burgering B. M., Bos J. L. Shc associates with an unphosphorylated form of the p21ras guanine nucleotide exchange factor mSOS. Oncogene. 1995 Mar 2;10(5):919–925. [PubMed] [Google Scholar]
  228. van Biesen T., Hawes B. E., Luttrell D. K., Krueger K. M., Touhara K., Porfiri E., Sakaue M., Luttrell L. M., Lefkowitz R. J. Receptor-tyrosine-kinase- and G beta gamma-mediated MAP kinase activation by a common signalling pathway. Nature. 1995 Aug 31;376(6543):781–784. doi: 10.1038/376781a0. [DOI] [PubMed] [Google Scholar]
  229. van der Geer P., Hunter T., Lindberg R. A. Receptor protein-tyrosine kinases and their signal transduction pathways. Annu Rev Cell Biol. 1994;10:251–337. doi: 10.1146/annurev.cb.10.110194.001343. [DOI] [PubMed] [Google Scholar]
  230. van der Geer P., Pawson T. The PTB domain: a new protein module implicated in signal transduction. Trends Biochem Sci. 1995 Jul;20(7):277–280. doi: 10.1016/s0968-0004(00)89043-x. [DOI] [PubMed] [Google Scholar]

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