Abstract
The effect of phorbol esters on the extent of phosphorylation of receptors for insulin and somatomedin C (insulin-like growth factor I) was studied in intact IM-9 cells that were labeled by incubation with H332PO4. The tumor-promoting phorbol esters phorbol tetradecanoate acetate (TPA) and phorbol dibutyrate, but not the inactive 4 alpha-phorbol, enhanced phosphorylation of the beta subunit of both receptors approximately 4-fold; 70 nM TPA maximally stimulated phosphorylation of both receptors, whereas concentrations less than or equal to 0.7 nM had no observable effect. Insulin also enhanced the phosphorylation of the beta subunit of the insulin receptor, and its effects appeared to be additive to those of TPA. Peptide maps indicated that at least some of the residues phosphorylated by these two agents are distinct. These results suggest a possible role of protein kinase C in regulating insulin and somatomedin C receptors.
Full text
PDF


Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
- Cleveland D. W., Fischer S. G., Kirschner M. W., Laemmli U. K. Peptide mapping by limited proteolysis in sodium dodecyl sulfate and analysis by gel electrophoresis. J Biol Chem. 1977 Feb 10;252(3):1102–1106. [PubMed] [Google Scholar]
- Driedger P. E., Blumberg P. M. Specific binding of phorbol ester tumor promoters. Proc Natl Acad Sci U S A. 1980 Jan;77(1):567–571. doi: 10.1073/pnas.77.1.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grunberger G., Gorden P. Affinity alteration of insulin receptor induced by a phorbol ester. Am J Physiol. 1982 Oct;243(4):E319–E324. doi: 10.1152/ajpendo.1982.243.4.E319. [DOI] [PubMed] [Google Scholar]
- Jacobs S., Chang K. J., Cuatrecasas P. Antibodies to purified insulin receptor have insulin-like activity. Science. 1978 Jun 16;200(4347):1283–1284. doi: 10.1126/science.663609. [DOI] [PubMed] [Google Scholar]
- Kasuga M., Karlsson F. A., Kahn C. R. Insulin stimulates the phosphorylation of the 95,000-dalton subunit of its own receptor. Science. 1982 Jan 8;215(4529):185–187. doi: 10.1126/science.7031900. [DOI] [PubMed] [Google Scholar]
- Kull F. C., Jr, Jacobs S., Su Y. F., Cuatrecasas P. A monoclonal antibody to human insulin receptor. Biochem Biophys Res Commun. 1982 Jun 15;106(3):1019–1026. doi: 10.1016/0006-291x(82)91813-7. [DOI] [PubMed] [Google Scholar]
- Kull F. C., Jr, Jacobs S., Su Y. F., Svoboda M. E., Van Wyk J. J., Cuatrecasas P. Monoclonal antibodies to receptors for insulin and somatomedin-C. J Biol Chem. 1983 May 25;258(10):6561–6566. [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Lee L. S., Weinstein I. B. Mechanism of tumor promoter inhibition of cellular binding of epidermal growth factor. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5168–5172. doi: 10.1073/pnas.76.10.5168. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Niedel J. E., Kuhn L. J., Vandenbark G. R. Phorbol diester receptor copurifies with protein kinase C. Proc Natl Acad Sci U S A. 1983 Jan;80(1):36–40. doi: 10.1073/pnas.80.1.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shoyab M., De Larco J. E., Todaro G. J. Biologically active phorbol esters specifically alter affinity of epidermal growth factor membrane receptors. Nature. 1979 May 31;279(5712):387–391. doi: 10.1038/279387a0. [DOI] [PubMed] [Google Scholar]
- Shoyab M., Todaro G. J. Specific high affinity cell membrane receptors for biologically active phorbol and ingenol esters. Nature. 1980 Dec 4;288(5790):451–455. doi: 10.1038/288451a0. [DOI] [PubMed] [Google Scholar]
- Thomopoulos P., Testa U., Gourdin M. F., Hervy C., Titeux M., Vainchenker W. Inhibition of insulin receptor binding by phorbol esters. Eur J Biochem. 1982 Dec 15;129(2):389–393. doi: 10.1111/j.1432-1033.1982.tb07062.x. [DOI] [PubMed] [Google Scholar]