Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1994 Jun 15;13(12):2831–2841. doi: 10.1002/j.1460-2075.1994.tb06577.x

Identification of c-erbB-3 binding sites for phosphatidylinositol 3'-kinase and SHC using an EGF receptor/c-erbB-3 chimera.

S A Prigent 1, W J Gullick 1
PMCID: PMC395164  PMID: 8026468

Abstract

c-erbB-3 is a member of the type I (EGF receptor-related) family of growth factor receptors for which no ligand has been identified. To facilitate ligand stimulation we have constructed a chimeric receptor which possesses an activatable kinase and promotes the growth of NIH 3T3 fibroblasts. In this study we have shown that SHC and phosphatidylinositol 3'-kinase bind to the activated EGF receptor/c-erbB-3 chimera. Whereas p85 is not phosphorylated to a significant extent, SHC appears to be a major substrate for phosphorylation on tyrosine. In contrast to EGF receptor and c-erbB-2, we were unable to detect binding of activated c-erbB-3 to GRB2. Using synthetic peptides corresponding to each of 13 potential phosphorylation sites on c-erbB-3, we have shown that tyrosine 1309 is responsible for SHC binding. Peptides containing the motif YXXM inhibit p85 association. By comparison with recently reported SHC binding sites on Middle T antigen and Trk we have identified a SHC binding motif, NPXY.

Full text

PDF
2834

Images in this article

2832Image
on p.2832
2832Image
on p.2832
2832Image
on p.2832
2833Image
on p.2833
2834Image
on p.2834
2835Image
on p.2835
2835Image
on p.2835
2835Image
on p.2835
2836Image
on p.2836
2837Image
on p.2837

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aaronson S. A. Growth factors and cancer. Science. 1991 Nov 22;254(5035):1146–1153. doi: 10.1126/science.1659742. [DOI] [PubMed] [Google Scholar]
  2. Aharonov A., Pruss R. M., Herschman H. R. Epidermal growth factor. Relationship between receptor regulation and mitogenesis in 3T3 cells. J Biol Chem. 1978 Jun 10;253(11):3970–3977. [PubMed] [Google Scholar]
  3. Bar-Sagi D., Rotin D., Batzer A., Mandiyan V., Schlessinger J. SH3 domains direct cellular localization of signaling molecules. Cell. 1993 Jul 16;74(1):83–91. doi: 10.1016/0092-8674(93)90296-3. [DOI] [PubMed] [Google Scholar]
  4. Buday L., Downward J. Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor. Cell. 1993 May 7;73(3):611–620. doi: 10.1016/0092-8674(93)90146-h. [DOI] [PubMed] [Google Scholar]
  5. Chardin P., Camonis J. H., Gale N. W., van Aelst L., Schlessinger J., Wigler M. H., Bar-Sagi D. Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2. Science. 1993 May 28;260(5112):1338–1343. doi: 10.1126/science.8493579. [DOI] [PubMed] [Google Scholar]
  6. Clark S. G., Stern M. J., Horvitz H. R. C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domains. Nature. 1992 Mar 26;356(6367):340–344. doi: 10.1038/356340a0. [DOI] [PubMed] [Google Scholar]
  7. Di Fiore P. P., Pierce J. H., Fleming T. P., Hazan R., Ullrich A., King C. R., Schlessinger J., Aaronson S. A. Overexpression of the human EGF receptor confers an EGF-dependent transformed phenotype to NIH 3T3 cells. Cell. 1987 Dec 24;51(6):1063–1070. doi: 10.1016/0092-8674(87)90592-7. [DOI] [PubMed] [Google Scholar]
  8. Di Fiore P. P., Pierce J. H., Kraus M. H., Segatto O., King C. R., Aaronson S. A. erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. Science. 1987 Jul 10;237(4811):178–182. doi: 10.1126/science.2885917. [DOI] [PubMed] [Google Scholar]
  9. Dilworth S. M., Brewster C. E., Jones M. D., Lanfrancone L., Pelicci G., Pelicci P. G. Transformation by polyoma virus middle T-antigen involves the binding and tyrosine phosphorylation of Shc. Nature. 1994 Jan 6;367(6458):87–90. doi: 10.1038/367087a0. [DOI] [PubMed] [Google Scholar]
  10. Egan S. E., Giddings B. W., Brooks M. W., Buday L., Sizeland A. M., Weinberg R. A. Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation. Nature. 1993 May 6;363(6424):45–51. doi: 10.1038/363045a0. [DOI] [PubMed] [Google Scholar]
  11. Escobedo J. A., Navankasattusas S., Kavanaugh W. M., Milfay D., Fried V. A., Williams L. T. cDNA cloning of a novel 85 kd protein that has SH2 domains and regulates binding of PI3-kinase to the PDGF beta-receptor. Cell. 1991 Apr 5;65(1):75–82. doi: 10.1016/0092-8674(91)90409-r. [DOI] [PubMed] [Google Scholar]
  12. Fantl W. J., Escobedo J. A., Martin G. A., Turck C. W., del Rosario M., McCormick F., Williams L. T. Distinct phosphotyrosines on a growth factor receptor bind to specific molecules that mediate different signaling pathways. Cell. 1992 May 1;69(3):413–423. doi: 10.1016/0092-8674(92)90444-h. [DOI] [PubMed] [Google Scholar]
  13. Feng G. S., Hui C. C., Pawson T. SH2-containing phosphotyrosine phosphatase as a target of protein-tyrosine kinases. Science. 1993 Mar 12;259(5101):1607–1611. doi: 10.1126/science.8096088. [DOI] [PubMed] [Google Scholar]
  14. Freeman R. M., Jr, Plutzky J., Neel B. G. Identification of a human src homology 2-containing protein-tyrosine-phosphatase: a putative homolog of Drosophila corkscrew. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11239–11243. doi: 10.1073/pnas.89.23.11239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gale N. W., Kaplan S., Lowenstein E. J., Schlessinger J., Bar-Sagi D. Grb2 mediates the EGF-dependent activation of guanine nucleotide exchange on Ras. Nature. 1993 May 6;363(6424):88–92. doi: 10.1038/363088a0. [DOI] [PubMed] [Google Scholar]
  16. Giard D. J., Aaronson S. A., Todaro G. J., Arnstein P., Kersey J. H., Dosik H., Parks W. P. In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst. 1973 Nov;51(5):1417–1423. doi: 10.1093/jnci/51.5.1417. [DOI] [PubMed] [Google Scholar]
  17. Gluzman Y. SV40-transformed simian cells support the replication of early SV40 mutants. Cell. 1981 Jan;23(1):175–182. doi: 10.1016/0092-8674(81)90282-8. [DOI] [PubMed] [Google Scholar]
  18. Goldman R., Levy R. B., Peles E., Yarden Y. Heterodimerization of the erbB-1 and erbB-2 receptors in human breast carcinoma cells: a mechanism for receptor transregulation. Biochemistry. 1990 Dec 18;29(50):11024–11028. doi: 10.1021/bi00502a002. [DOI] [PubMed] [Google Scholar]
  19. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  20. Gullick W. J., Berger M. S., Bennett P. L., Rothbard J. B., Waterfield M. D. Expression of the c-erbB-2 protein in normal and transformed cells. Int J Cancer. 1987 Aug 15;40(2):246–254. doi: 10.1002/ijc.2910400221. [DOI] [PubMed] [Google Scholar]
  21. Gullick W. J., Downward J., Waterfield M. D. Antibodies to the autophosphorylation sites of the epidermal growth factor receptor protein-tyrosine kinase as probes of structure and function. EMBO J. 1985 Nov;4(11):2869–2877. doi: 10.1002/j.1460-2075.1985.tb04016.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gullick W. J. Prevalence of aberrant expression of the epidermal growth factor receptor in human cancers. Br Med Bull. 1991 Jan;47(1):87–98. doi: 10.1093/oxfordjournals.bmb.a072464. [DOI] [PubMed] [Google Scholar]
  23. Hanks S. K., Quinn A. M., Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science. 1988 Jul 1;241(4861):42–52. doi: 10.1126/science.3291115. [DOI] [PubMed] [Google Scholar]
  24. Hu P., Margolis B., Skolnik E. Y., Lammers R., Ullrich A., Schlessinger J. Interaction of phosphatidylinositol 3-kinase-associated p85 with epidermal growth factor and platelet-derived growth factor receptors. Mol Cell Biol. 1992 Mar;12(3):981–990. doi: 10.1128/mcb.12.3.981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hudziak R. M., Schlessinger J., Ullrich A. Increased expression of the putative growth factor receptor p185HER2 causes transformation and tumorigenesis of NIH 3T3 cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7159–7163. doi: 10.1073/pnas.84.20.7159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Jainchill J. L., Aaronson S. A., Todaro G. J. Murine sarcoma and leukemia viruses: assay using clonal lines of contact-inhibited mouse cells. J Virol. 1969 Nov;4(5):549–553. doi: 10.1128/jvi.4.5.549-553.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kamps M. P., Sefton B. M. Acid and base hydrolysis of phosphoproteins bound to immobilon facilitates analysis of phosphoamino acids in gel-fractionated proteins. Anal Biochem. 1989 Jan;176(1):22–27. doi: 10.1016/0003-2697(89)90266-2. [DOI] [PubMed] [Google Scholar]
  28. Knighton D. R., Zheng J. H., Ten Eyck L. F., Ashford V. A., Xuong N. H., Taylor S. S., Sowadski J. M. Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. Science. 1991 Jul 26;253(5018):407–414. doi: 10.1126/science.1862342. [DOI] [PubMed] [Google Scholar]
  29. Kraus M. H., Fedi P., Starks V., Muraro R., Aaronson S. A. Demonstration of ligand-dependent signaling by the erbB-3 tyrosine kinase and its constitutive activation in human breast tumor cells. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2900–2904. doi: 10.1073/pnas.90.7.2900. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kraus M. H., Issing W., Miki T., Popescu N. C., Aaronson S. A. Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9193–9197. doi: 10.1073/pnas.86.23.9193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kumar R., Shepard H. M., Mendelsohn J. Regulation of phosphorylation of the c-erbB-2/HER2 gene product by a monoclonal antibody and serum growth factor(s) in human mammary carcinoma cells. Mol Cell Biol. 1991 Feb;11(2):979–986. doi: 10.1128/mcb.11.2.979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lehväslaiho H., Lehtola L., Sistonen L., Alitalo K. A chimeric EGF-R-neu proto-oncogene allows EGF to regulate neu tyrosine kinase and cell transformation. EMBO J. 1989 Jan;8(1):159–166. doi: 10.1002/j.1460-2075.1989.tb03360.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Lehväslaiho H., Sistonen L., diRenzo F., Partanen J., Comoglio P., Hölttä E., Alitalo K. Regulation by EGF is maintained in an overexpressed chimeric EGFR/neu receptor tyrosine kinase. J Cell Biochem. 1990 Mar;42(3):123–133. doi: 10.1002/jcb.240420303. [DOI] [PubMed] [Google Scholar]
  34. Lemoine N. R., Barnes D. M., Hollywood D. P., Hughes C. M., Smith P., Dublin E., Prigent S. A., Gullick W. J., Hurst H. C. Expression of the ERBB3 gene product in breast cancer. Br J Cancer. 1992 Dec;66(6):1116–1121. doi: 10.1038/bjc.1992.420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Lemoine N. R., Lobresco M., Leung H., Barton C., Hughes C. M., Prigent S. A., Gullick W. J., Klöppel G. The erbB-3 gene in human pancreatic cancer. J Pathol. 1992 Nov;168(3):269–273. doi: 10.1002/path.1711680305. [DOI] [PubMed] [Google Scholar]
  36. Lemoine N. R., Mayall E. S., Jones T., Sheer D., McDermid S., Kendall-Taylor P., Wynford-Thomas D. Characterisation of human thyroid epithelial cells immortalised in vitro by simian virus 40 DNA transfection. Br J Cancer. 1989 Dec;60(6):897–903. doi: 10.1038/bjc.1989.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Li N., Batzer A., Daly R., Yajnik V., Skolnik E., Chardin P., Bar-Sagi D., Margolis B., Schlessinger J. Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling. Nature. 1993 May 6;363(6424):85–88. doi: 10.1038/363085a0. [DOI] [PubMed] [Google Scholar]
  38. Livneh E., Benveniste M., Prywes R., Felder S., Kam Z., Schlessinger J. Large deletions in the cytoplasmic kinase domain of the epidermal growth factor receptor do not affect its laternal mobility. J Cell Biol. 1986 Aug;103(2):327–331. doi: 10.1083/jcb.103.2.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Lowenstein E. J., Daly R. J., Batzer A. G., Li W., Margolis B., Lammers R., Ullrich A., Skolnik E. Y., Bar-Sagi D., Schlessinger J. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell. 1992 Aug 7;70(3):431–442. doi: 10.1016/0092-8674(92)90167-b. [DOI] [PubMed] [Google Scholar]
  40. McGlade J., Cheng A., Pelicci G., Pelicci P. G., Pawson T. Shc proteins are phosphorylated and regulated by the v-Src and v-Fps protein-tyrosine kinases. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):8869–8873. doi: 10.1073/pnas.89.19.8869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Moran M. F., Koch C. A., Sadowski I., Pawson T. Mutational analysis of a phosphotransfer motif essential for v-fps tyrosine kinase activity. Oncogene. 1988 Dec;3(6):665–672. [PubMed] [Google Scholar]
  42. Morgan S. J., Smith A. D., Parker P. J. Purification and characterization of bovine brain type I phosphatidylinositol kinase. Eur J Biochem. 1990 Aug 17;191(3):761–767. doi: 10.1111/j.1432-1033.1990.tb19185.x. [DOI] [PubMed] [Google Scholar]
  43. Obermeier A., Lammers R., Wiesmüller K. H., Jung G., Schlessinger J., Ullrich A. Identification of Trk binding sites for SHC and phosphatidylinositol 3'-kinase and formation of a multimeric signaling complex. J Biol Chem. 1993 Nov 5;268(31):22963–22966. [PubMed] [Google Scholar]
  44. Olivier J. P., Raabe T., Henkemeyer M., Dickson B., Mbamalu G., Margolis B., Schlessinger J., Hafen E., Pawson T. A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos. Cell. 1993 Apr 9;73(1):179–191. doi: 10.1016/0092-8674(93)90170-u. [DOI] [PubMed] [Google Scholar]
  45. Pawson T., Schlessingert J. SH2 and SH3 domains. Curr Biol. 1993 Jul 1;3(7):434–442. doi: 10.1016/0960-9822(93)90350-w. [DOI] [PubMed] [Google Scholar]
  46. Pelicci G., Lanfrancone L., Grignani F., McGlade J., Cavallo F., Forni G., Nicoletti I., Grignani F., Pawson T., Pelicci P. G. A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction. Cell. 1992 Jul 10;70(1):93–104. doi: 10.1016/0092-8674(92)90536-l. [DOI] [PubMed] [Google Scholar]
  47. Pillay T. S., Makgoba M. W. Enhancement of epidermal growth factor (EGF) and insulin-stimulated tyrosine phosphorylation of endogenous substrates by sodium selenate. FEBS Lett. 1992 Aug 10;308(1):38–42. doi: 10.1016/0014-5793(92)81045-n. [DOI] [PubMed] [Google Scholar]
  48. Plowman G. D., Culouscou J. M., Whitney G. S., Green J. M., Carlton G. W., Foy L., Neubauer M. G., Shoyab M. Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1746–1750. doi: 10.1073/pnas.90.5.1746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Plowman G. D., Whitney G. S., Neubauer M. G., Green J. M., McDonald V. L., Todaro G. J., Shoyab M. Molecular cloning and expression of an additional epidermal growth factor receptor-related gene. Proc Natl Acad Sci U S A. 1990 Jul;87(13):4905–4909. doi: 10.1073/pnas.87.13.4905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Prigent S. A., Lemoine N. R., Hughes C. M., Plowman G. D., Selden C., Gullick W. J. Expression of the c-erbB-3 protein in normal human adult and fetal tissues. Oncogene. 1992 Jul;7(7):1273–1278. [PubMed] [Google Scholar]
  51. Rajkumar T., Gooden C. S., Lemoine N. R., Gullick W. J., Goden C. S. Expression of the c-erbB-3 protein in gastrointestinal tract tumours determined by monoclonal antibody RTJ1. J Pathol. 1993 Jul;170(3):271–278. doi: 10.1002/path.1711700309. [DOI] [PubMed] [Google Scholar]
  52. Riedel H., Dull T. J., Schlessinger J., Ullrich A. A chimaeric receptor allows insulin to stimulate tyrosine kinase activity of epidermal growth factor receptor. Nature. 1986 Nov 6;324(6092):68–70. doi: 10.1038/324068a0. [DOI] [PubMed] [Google Scholar]
  53. Rozakis-Adcock M., Fernley R., Wade J., Pawson T., Bowtell D. The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1. Nature. 1993 May 6;363(6424):83–85. doi: 10.1038/363083a0. [DOI] [PubMed] [Google Scholar]
  54. Rozakis-Adcock M., McGlade J., Mbamalu G., Pelicci G., Daly R., Li W., Batzer A., Thomas S., Brugge J., Pelicci P. G. Association of the Shc and Grb2/Sem5 SH2-containing proteins is implicated in activation of the Ras pathway by tyrosine kinases. Nature. 1992 Dec 17;360(6405):689–692. doi: 10.1038/360689a0. [DOI] [PubMed] [Google Scholar]
  55. Schägger H., von Jagow G. Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal Biochem. 1987 Nov 1;166(2):368–379. doi: 10.1016/0003-2697(87)90587-2. [DOI] [PubMed] [Google Scholar]
  56. Seedorf K., Felder S., Millauer B., Schlessinger J., Ullrich A. Analysis of platelet-derived growth factor receptor domain function using a novel chimeric receptor approach. J Biol Chem. 1991 Jul 5;266(19):12424–12431. [PubMed] [Google Scholar]
  57. Segatto O., Pelicci G., Giuli S., Digiesi G., Di Fiore P. P., McGlade J., Pawson T., Pelicci P. G. Shc products are substrates of erbB-2 kinase. Oncogene. 1993 Aug;8(8):2105–2112. [PubMed] [Google Scholar]
  58. Shen S. H., Bastien L., Posner B. I., Chrétien P. A protein-tyrosine phosphatase with sequence similarity to the SH2 domain of the protein-tyrosine kinases. Nature. 1991 Aug 22;352(6337):736–739. doi: 10.1038/352736a0. [DOI] [PubMed] [Google Scholar]
  59. Simon M. A., Dodson G. S., Rubin G. M. An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro. Cell. 1993 Apr 9;73(1):169–177. doi: 10.1016/0092-8674(93)90169-q. [DOI] [PubMed] [Google Scholar]
  60. Songyang Z., Shoelson S. E., Chaudhuri M., Gish G., Pawson T., Haser W. G., King F., Roberts T., Ratnofsky S., Lechleider R. J. SH2 domains recognize specific phosphopeptide sequences. Cell. 1993 Mar 12;72(5):767–778. doi: 10.1016/0092-8674(93)90404-e. [DOI] [PubMed] [Google Scholar]
  61. Stahl M. L., Ferenz C. R., Kelleher K. L., Kriz R. W., Knopf J. L. Sequence similarity of phospholipase C with the non-catalytic region of src. Nature. 1988 Mar 17;332(6161):269–272. doi: 10.1038/332269a0. [DOI] [PubMed] [Google Scholar]
  62. Suen K. L., Bustelo X. R., Pawson T., Barbacid M. Molecular cloning of the mouse grb2 gene: differential interaction of the Grb2 adaptor protein with epidermal growth factor and nerve growth factor receptors. Mol Cell Biol. 1993 Sep;13(9):5500–5512. doi: 10.1128/mcb.13.9.5500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Tan J. C., Nocka K., Ray P., Traktman P., Besmer P. The dominant W42 spotting phenotype results from a missense mutation in the c-kit receptor kinase. Science. 1990 Jan 12;247(4939):209–212. doi: 10.1126/science.1688471. [DOI] [PubMed] [Google Scholar]
  64. Trahey M., Wong G., Halenbeck R., Rubinfeld B., Martin G. A., Ladner M., Long C. M., Crosier W. J., Watt K., Koths K. Molecular cloning of two types of GAP complementary DNA from human placenta. Science. 1988 Dec 23;242(4886):1697–1700. doi: 10.1126/science.3201259. [DOI] [PubMed] [Google Scholar]
  65. Valius M., Kazlauskas A. Phospholipase C-gamma 1 and phosphatidylinositol 3 kinase are the downstream mediators of the PDGF receptor's mitogenic signal. Cell. 1993 Apr 23;73(2):321–334. doi: 10.1016/0092-8674(93)90232-f. [DOI] [PubMed] [Google Scholar]
  66. Vogel W., Lammers R., Huang J., Ullrich A. Activation of a phosphotyrosine phosphatase by tyrosine phosphorylation. Science. 1993 Mar 12;259(5101):1611–1614. doi: 10.1126/science.7681217. [DOI] [PubMed] [Google Scholar]
  67. Walsh J. P., Caldwell K. K., Majerus P. W. Formation of phosphatidylinositol 3-phosphate by isomerization from phosphatidylinositol 4-phosphate. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9184–9187. doi: 10.1073/pnas.88.20.9184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Waterfield M. D., Mayes E. L., Stroobant P., Bennet P. L., Young S., Goodfellow P. N., Banting G. S., Ozanne B. A monoclonal antibody to the human epidermal growth factor receptor. J Cell Biochem. 1982;20(2):149–161. doi: 10.1002/jcb.240200207. [DOI] [PubMed] [Google Scholar]
  69. Whitman M., Kaplan D. R., Schaffhausen B., Cantley L., Roberts T. M. Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation. Nature. 1985 May 16;315(6016):239–242. doi: 10.1038/315239a0. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES