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. 1987 Nov;7(11):4146–4149. doi: 10.1128/mcb.7.11.4146

Involvement of functional protein kinase C in the mitogenic response to the H-ras oncogene product.

J C Lacal 1, T P Fleming 1, B S Warren 1, P M Blumberg 1, S A Aaronson 1
PMCID: PMC368090  PMID: 3323889

Abstract

Microinjection of purified protein kinase C (PKC) into Swiss 3T3 fibroblasts pretreated with the phorbol ester phorbol-12,13-dibutyrate restores the mitogenic response of the cells to phorbol-12,13-dibutyrate (G. Pasti, J.C. Lacal, B.S. Warren, S.A. Aaronson, and P.M. Blumberg, Nature [London] 324:375-377, 1986). Our present studies demonstrate that the mitogenic activity of the H-ras oncogene in H-ras p21-microinjected quiescent cells is markedly reduced under conditions in which PKC is downregulated by chronic phorbol ester treatment. The ability to reconstitute the mitogenic response upon microinjection of both H-ras p21 and PKC implies involvement of functional PKC in the mitogenic activity of the H-ras oncogene product.

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Selected References

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

  1. Collins M. K., Rozengurt E. Binding of phorbol esters to high-affinity sites on murine fibroblastic cells elicits a mitogenic response. J Cell Physiol. 1982 Jul;112(1):42–50. doi: 10.1002/jcp.1041120108. [DOI] [PubMed] [Google Scholar]
  2. Collins M. K., Rozengurt E. Homologous and heterologous mitogenic desensitization of Swiss 3T3 cells to phorbol esters and vasopressin: role of receptor and postreceptor steps. J Cell Physiol. 1984 Feb;118(2):133–142. doi: 10.1002/jcp.1041180205. [DOI] [PubMed] [Google Scholar]
  3. Feramisco J. R., Gross M., Kamata T., Rosenberg M., Sweet R. W. Microinjection of the oncogene form of the human H-ras (T-24) protein results in rapid proliferation of quiescent cells. Cell. 1984 Aug;38(1):109–117. doi: 10.1016/0092-8674(84)90531-2. [DOI] [PubMed] [Google Scholar]
  4. Fleischman L. F., Chahwala S. B., Cantley L. ras-transformed cells: altered levels of phosphatidylinositol-4,5-bisphosphate and catabolites. Science. 1986 Jan 24;231(4736):407–410. doi: 10.1126/science.3001936. [DOI] [PubMed] [Google Scholar]
  5. Hagag N., Lacal J. C., Graber M., Aaronson S., Viola M. V. Microinjection of ras p21 induces a rapid rise in intracellular pH. Mol Cell Biol. 1987 May;7(5):1984–1988. doi: 10.1128/mcb.7.5.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Lacal J. C., Srivastava S. K., Anderson P. S., Aaronson S. A. Ras p21 proteins with high or low GTPase activity can efficiently transform NIH/3T3 cells. Cell. 1986 Feb 28;44(4):609–617. doi: 10.1016/0092-8674(86)90270-9. [DOI] [PubMed] [Google Scholar]
  7. Majerus P. W., Connolly T. M., Deckmyn H., Ross T. S., Bross T. E., Ishii H., Bansal V. S., Wilson D. B. The metabolism of phosphoinositide-derived messenger molecules. Science. 1986 Dec 19;234(4783):1519–1526. doi: 10.1126/science.3024320. [DOI] [PubMed] [Google Scholar]
  8. Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
  9. Pasti G., Lacal J. C., Warren B. S., Aaronson S. A., Blumberg P. M. Loss of mouse fibroblast cell response to phorbol esters restored by microinjected protein kinase C. 1986 Nov 27-Dec 3Nature. 324(6095):375–377. doi: 10.1038/324375a0. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Stacey D. W., Kung H. F. Transformation of NIH 3T3 cells by microinjection of Ha-ras p21 protein. Nature. 1984 Aug 9;310(5977):508–511. doi: 10.1038/310508a0. [DOI] [PubMed] [Google Scholar]
  12. Vara F., Rozengurt E. Stimulation of Na+/H+ antiport activity by epidermal growth factor and insulin occurs without activation of protein kinase C. Biochem Biophys Res Commun. 1985 Jul 31;130(2):646–653. doi: 10.1016/0006-291x(85)90466-8. [DOI] [PubMed] [Google Scholar]
  13. Willecke K., Schäfer R. Human oncogenes. Hum Genet. 1984;66(2-3):132–142. doi: 10.1007/BF00286587. [DOI] [PubMed] [Google Scholar]
  14. Wolfman A., Macara I. G. Elevated levels of diacylglycerol and decreased phorbol ester sensitivity in ras-transformed fibroblasts. Nature. 1987 Jan 22;325(6102):359–361. doi: 10.1038/325359a0. [DOI] [PubMed] [Google Scholar]

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