Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Mar 28;92(7):2592–2596. doi: 10.1073/pnas.92.7.2592

Activation of YRP kinase by v-Src and protein kinase C-mediated signal transduction pathways.

G Scholz 1, M P Felder 1, H Hanafusa 1
PMCID: PMC42264  PMID: 7535926

Abstract

We have previously reported that a serine(threonine) protein kinase that phosphorylates histone H1 in vitro is activated by tyrosine phosphorylation in v-Src-transformed rat 3Y1 fibroblasts. We now refer to this kinase as YRP kinase, for tyrosine-regulated protein kinase. Since YRP kinase may play a role in mediating the growth-stimulatory and morphology-altering effects of v-Src, we have further examined the signal transduction involved in the activation of YRP kinase. Although YRP kinase is constitutively activated in fibroblasts transformed by v-Src, activation of protein kinase C was also found to lead to activation of YRP kinase. Activation of YRP kinase by protein kinase C was found to be potentiated by vanadate treatment or overexpression of c-Src. The activation of YRP kinase by v-Src, however, does not appear to be mediated by protein kinase C, suggesting that YRP kinase can be activated by two separate signal transduction pathways. Transformation of fibroblasts by v-Ras or v-Mil did not result in activation of YRP kinase, indicating that the MAP kinase pathway does not mediate the activation of YRP kinase by v-Src or protein kinase C.

Full text

PDF
2592

Images in this article

2594Fig. 3
on p.2594

Selected References

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

  1. Adams P. D., Parker P. J. TPA-induced activation of MAP kinase. FEBS Lett. 1991 Sep 23;290(1-2):77–82. doi: 10.1016/0014-5793(91)81230-6. [DOI] [PubMed] [Google Scholar]
  2. Brott B. K., Decker S., Shafer J., Gibbs J. B., Jove R. GTPase-activating protein interactions with the viral and cellular Src kinases. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):755–759. doi: 10.1073/pnas.88.3.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cantley L. C., Auger K. R., Carpenter C., Duckworth B., Graziani A., Kapeller R., Soltoff S. Oncogenes and signal transduction. Cell. 1991 Jan 25;64(2):281–302. doi: 10.1016/0092-8674(91)90639-g. [DOI] [PubMed] [Google Scholar]
  4. Chiarugi V., Porciatti F., Pasquali F., Magnelli L., Giannelli S., Ruggiero M. Polyphosphoinositide metabolism is rapidly stimulated by activation of a temperature-sensitive mutant of Rous sarcoma virus in rat fibroblasts. Oncogene. 1987;2(1):37–40. [PubMed] [Google Scholar]
  5. Cross F. R., Hanafusa H. Local mutagenesis of Rous sarcoma virus: the major sites of tyrosine and serine phosphorylation of pp60src are dispensable for transformation. Cell. 1983 Sep;34(2):597–607. doi: 10.1016/0092-8674(83)90392-6. [DOI] [PubMed] [Google Scholar]
  6. Gilmore T., Martin G. S. Phorbol ester and diacylglycerol induce protein phosphorylation at tyrosine. Nature. 1983 Dec 1;306(5942):487–490. doi: 10.1038/306487a0. [DOI] [PubMed] [Google Scholar]
  7. Glenney J. R., Jr, Zokas L. Novel tyrosine kinase substrates from Rous sarcoma virus-transformed cells are present in the membrane skeleton. J Cell Biol. 1989 Jun;108(6):2401–2408. doi: 10.1083/jcb.108.6.2401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gould K. L., Woodgett J. R., Cooper J. A., Buss J. E., Shalloway D., Hunter T. Protein kinase C phosphorylates pp60src at a novel site. Cell. 1985 Oct;42(3):849–857. doi: 10.1016/0092-8674(85)90281-8. [DOI] [PubMed] [Google Scholar]
  9. Gupta S. K., Gallego C., Johnson G. L., Heasley L. E. MAP kinase is constitutively activated in gip2 and src transformed rat 1a fibroblasts. J Biol Chem. 1992 Apr 25;267(12):7987–7990. [PubMed] [Google Scholar]
  10. Hanafusa H. Rapid transformation of cells by Rous sarcoma virus. Proc Natl Acad Sci U S A. 1969 Jun;63(2):318–325. doi: 10.1073/pnas.63.2.318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hirst R., Horwitz A., Buck C., Rohrschneider L. Phosphorylation of the fibronectin receptor complex in cells transformed by oncogenes that encode tyrosine kinases. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6470–6474. doi: 10.1073/pnas.83.17.6470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. House C., Kemp B. E. Protein kinase C contains a pseudosubstrate prototope in its regulatory domain. Science. 1987 Dec 18;238(4834):1726–1728. doi: 10.1126/science.3686012. [DOI] [PubMed] [Google Scholar]
  13. Hunter T., Cooper J. A. Protein-tyrosine kinases. Annu Rev Biochem. 1985;54:897–930. doi: 10.1146/annurev.bi.54.070185.004341. [DOI] [PubMed] [Google Scholar]
  14. Jove R., Hanafusa H. Cell transformation by the viral src oncogene. Annu Rev Cell Biol. 1987;3:31–56. doi: 10.1146/annurev.cb.03.110187.000335. [DOI] [PubMed] [Google Scholar]
  15. Jove R., Mayer B. J., Iba H., Laugier D., Poirier F., Calothy G., Hanafusa T., Hanafusa H. Genetic analysis of p60v-src domains involved in the induction of different cell transformation parameters. J Virol. 1986 Dec;60(3):840–848. doi: 10.1128/jvi.60.3.840-848.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kawai S., Nishizawa M. New procedure for DNA transfection with polycation and dimethyl sulfoxide. Mol Cell Biol. 1984 Jun;4(6):1172–1174. doi: 10.1128/mcb.4.6.1172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kawamoto S., Hidaka H. 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine (H-7) is a selective inhibitor of protein kinase C in rabbit platelets. Biochem Biophys Res Commun. 1984 Nov 30;125(1):258–264. doi: 10.1016/s0006-291x(84)80362-9. [DOI] [PubMed] [Google Scholar]
  18. Kobayashi E., Nakano H., Morimoto M., Tamaoki T. Calphostin C (UCN-1028C), a novel microbial compound, is a highly potent and specific inhibitor of protein kinase C. Biochem Biophys Res Commun. 1989 Mar 15;159(2):548–553. doi: 10.1016/0006-291x(89)90028-4. [DOI] [PubMed] [Google Scholar]
  19. Kypta R. M., Goldberg Y., Ulug E. T., Courtneidge S. A. Association between the PDGF receptor and members of the src family of tyrosine kinases. Cell. 1990 Aug 10;62(3):481–492. doi: 10.1016/0092-8674(90)90013-5. [DOI] [PubMed] [Google Scholar]
  20. L'Allemain G., Sturgill T. W., Weber M. J. Defective regulation of mitogen-activated protein kinase activity in a 3T3 cell variant mitogenically nonresponsive to tetradecanoyl phorbol acetate. Mol Cell Biol. 1991 Feb;11(2):1002–1008. doi: 10.1128/mcb.11.2.1002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Levy J. B., Iba H., Hanafusa H. Activation of the transforming potential of p60c-src by a single amino acid change. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4228–4232. doi: 10.1073/pnas.83.12.4228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mayer B. J., Jove R., Krane J. F., Poirier F., Calothy G., Hanafusa H. Genetic lesions involved in temperature sensitivity of the src gene products of four Rous sarcoma virus mutants. J Virol. 1986 Dec;60(3):858–867. doi: 10.1128/jvi.60.3.858-867.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Moyers J. S., Bouton A. H., Parsons S. J. The sites of phosphorylation by protein kinase C and an intact SH2 domain are required for the enhanced response to beta-adrenergic agonists in cells overexpressing c-src. Mol Cell Biol. 1993 Apr;13(4):2391–2400. doi: 10.1128/mcb.13.4.2391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Radke K., Gilmore T., Martin G. S. Transformation by Rous sarcoma virus: a cellular substrate for transformation-specific protein phosphorylation contains phosphotyrosine. Cell. 1980 Oct;21(3):821–828. doi: 10.1016/0092-8674(80)90445-6. [DOI] [PubMed] [Google Scholar]
  25. Rodriguez-Pena A., Rozengurt E. Disappearance of Ca2+-sensitive, phospholipid-dependent protein kinase activity in phorbol ester-treated 3T3 cells. Biochem Biophys Res Commun. 1984 May 16;120(3):1053–1059. doi: 10.1016/s0006-291x(84)80213-2. [DOI] [PubMed] [Google Scholar]
  26. Sagara J., Yamada K. M., Kakunaga T. Induction of an unusual type of shared phosphorylation in human and avian cells by tumor-promoting phorbol esters or transformation. Cancer Res. 1986 Oct;46(10):5291–5296. [PubMed] [Google Scholar]
  27. Schaller M. D., Borgman C. A., Cobb B. S., Vines R. R., Reynolds A. B., Parsons J. T. pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5192–5196. doi: 10.1073/pnas.89.11.5192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sefton B. M., Hunter T., Ball E. H., Singer S. J. Vinculin: a cytoskeletal target of the transforming protein of Rous sarcoma virus. Cell. 1981 Apr;24(1):165–174. doi: 10.1016/0092-8674(81)90512-2. [DOI] [PubMed] [Google Scholar]
  29. Smith M. R., DeGudicibus S. J., Stacey D. W. Requirement for c-ras proteins during viral oncogene transformation. Nature. 1986 Apr 10;320(6062):540–543. doi: 10.1038/320540a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Spangler R., Joseph C., Qureshi S. A., Berg K. L., Foster D. A. Evidence that v-src and v-fps gene products use a protein kinase C-mediated pathway to induce expression of a transformation-related gene. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7017–7021. doi: 10.1073/pnas.86.18.7017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sternberg D. W., Scholz G., Fukui Y., Hanafusa H. Activation of a histone H1 kinase by tyrosine phosphorylation in v-src-transformed fibroblasts. EMBO J. 1993 Jan;12(1):323–330. doi: 10.1002/j.1460-2075.1993.tb05660.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wolfman A., Wingrove T. G., Blackshear P. J., Macara I. G. Down-regulation of protein kinase C and of an endogenous 80-kDa substrate in transformed fibroblasts. J Biol Chem. 1987 Dec 5;262(34):16546–16552. [PubMed] [Google Scholar]
  33. Yaciuk P., Choi J. K., Shalloway D. Mutation of amino acids in pp60c-src that are phosphorylated by protein kinases C and A. Mol Cell Biol. 1989 Jun;9(6):2453–2463. doi: 10.1128/mcb.9.6.2453. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES