Effects of transiently expressed atypical (zeta, lambda), conventional (alpha, beta) and novel (delta, epsilon) protein kinase C isoforms on insulin-stimulated translocation of epitope-tagged GLUT4 glucose transporters in rat adipocytes: specific interchangeable effects of protein kinases C-zeta and C-lambda (original) (raw)

. 1999 Feb 1;337(Pt 3):461–470.

Abstract

Atypical protein kinase (PK)C isoforms, zeta and lambda, have been reported to be activated by insulin via phosphoinositide 3-kinase, and have been suggested to be required for insulin-stimulated glucose transport. Here, we have examined the effects of transiently expressed wild-type (WT), constitutively active (Constit) and kinase-inactive (KI) forms of atypical PKCs, zeta and lambda, on haemagglutinin antigen (HAA)-tagged glucose transporter 4 (GLUT4) translocation in rat adipocytes, and compared these effects with each other and with those of comparable forms of conventional (alpha, beta) and novel (delta, epsilon) PKCs, which have also been proposed to be required for insulin-stimulated glucose transport. KI-PKC-zeta evoked consistent, sizeable (overall mean of 65%) inhibitory effects on insulin-stimulated, but not basal or guanosine-5'-[gamma-thio]triphosphate-stimulated, HAA-GLUT4 translocation; moreover, inhibitory effects of KI-PKC-zeta were largely reversed by co-transfection of WT-PKC-zeta. Like KI-PKC-zeta, KI-PKC-lambda inhibited insulin-stimulated HAA-GLUT4 translocation by approx. 40-60%, and the combination of KI-PKC-zeta and KI-PKC-lambda caused nearly complete (85%) inhibition. Of particular interest is the fact that inhibitory effects of KI forms of PKC-zeta and PKC-lambda were largely reversed by the opposite WT forms, i.e. PKC-lambda and PKC-zeta respectively. In contrast with KI forms of atypical PKCs, KI forms of PKC-alpha, PKC-beta2, PKC-delta and PKC-epsilon had little or no effect on insulin-stimulated HAA-GLUT4 translocation. Concerning the question of sufficiency, overexpression of WT-PKC-zeta enhanced insulin effects on HAA-GLUT4 translocation, whereas WT forms of PKC-alpha, PKC-beta2, PKC-delta and PKC-epsilon did not affect GLUT4 translocation; furthermore, Constit PKC-zeta evoked increases in HAA-GLUT4 translocation approaching those of insulin, but Constit forms of PKC-alpha and PKC-beta2 were without effect. Our findings suggest that, among PKCs, the atypical PKCs, zeta and lambda, appear to be specifically, but interchangeably, required for insulin effects on HAA-GLUT4 translocation.

Full Text

The Full Text of this article is available as a PDF (390.5 KB).

Selected References

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

  1. Akimoto K., Mizuno K., Osada S., Hirai S., Tanuma S., Suzuki K., Ohno S. A new member of the third class in the protein kinase C family, PKC lambda, expressed dominantly in an undifferentiated mouse embryonal carcinoma cell line and also in many tissues and cells. J Biol Chem. 1994 Apr 29;269(17):12677–12683. [PubMed] [Google Scholar]
  2. Alessi D. R., James S. R., Downes C. P., Holmes A. B., Gaffney P. R., Reese C. B., Cohen P. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha. Curr Biol. 1997 Apr 1;7(4):261–269. doi: 10.1016/s0960-9822(06)00122-9. [DOI] [PubMed] [Google Scholar]
  3. Bandyopadhyay G., Standaert M. L., Galloway L., Moscat J., Farese R. V. Evidence for involvement of protein kinase C (PKC)-zeta and noninvolvement of diacylglycerol-sensitive PKCs in insulin-stimulated glucose transport in L6 myotubes. Endocrinology. 1997 Nov;138(11):4721–4731. doi: 10.1210/endo.138.11.5473. [DOI] [PubMed] [Google Scholar]
  4. Bandyopadhyay G., Standaert M. L., Zhao L., Yu B., Avignon A., Galloway L., Karnam P., Moscat J., Farese R. V. Activation of protein kinase C (alpha, beta, and zeta) by insulin in 3T3/L1 cells. Transfection studies suggest a role for PKC-zeta in glucose transport. J Biol Chem. 1997 Jan 24;272(4):2551–2558. doi: 10.1074/jbc.272.4.2551. [DOI] [PubMed] [Google Scholar]
  5. Bossenmaier B., Mosthaf L., Mischak H., Ullrich A., Häring H. U. Protein kinase C isoforms beta 1 and beta 2 inhibit the tyrosine kinase activity of the insulin receptor. Diabetologia. 1997 Jul;40(7):863–866. doi: 10.1007/s001250050761. [DOI] [PubMed] [Google Scholar]
  6. Chalfant C. E., Ohno S., Konno Y., Fisher A. A., Bisnauth L. D., Watson J. E., Cooper D. R. A carboxy-terminal deletion mutant of protein kinase C beta II inhibits insulin-stimulated 2-deoxyglucose uptake in L6 rat skeletal muscle cells. Mol Endocrinol. 1996 Oct;10(10):1273–1281. doi: 10.1210/mend.10.10.9121494. [DOI] [PubMed] [Google Scholar]
  7. Cong L. N., Chen H., Li Y., Zhou L., McGibbon M. A., Taylor S. I., Quon M. J. Physiological role of Akt in insulin-stimulated translocation of GLUT4 in transfected rat adipose cells. Mol Endocrinol. 1997 Dec;11(13):1881–1890. doi: 10.1210/mend.11.13.0027. [DOI] [PubMed] [Google Scholar]
  8. Diaz-Meco M. T., Municio M. M., Sanchez P., Lozano J., Moscat J. Lambda-interacting protein, a novel protein that specifically interacts with the zinc finger domain of the atypical protein kinase C isotype lambda/iota and stimulates its kinase activity in vitro and in vivo. Mol Cell Biol. 1996 Jan;16(1):105–114. doi: 10.1128/mcb.16.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Franke T. F., Kaplan D. R., Cantley L. C., Toker A. Direct regulation of the Akt proto-oncogene product by phosphatidylinositol-3,4-bisphosphate. Science. 1997 Jan 31;275(5300):665–668. doi: 10.1126/science.275.5300.665. [DOI] [PubMed] [Google Scholar]
  10. Genot E. M., Parker P. J., Cantrell D. A. Analysis of the role of protein kinase C-alpha, -epsilon, and -zeta in T cell activation. J Biol Chem. 1995 Apr 28;270(17):9833–9839. doi: 10.1074/jbc.270.17.9833. [DOI] [PubMed] [Google Scholar]
  11. Konishi H., Kuroda S., Kikkawa U. The pleckstrin homology domain of RAC protein kinase associates with the regulatory domain of protein kinase C zeta. Biochem Biophys Res Commun. 1994 Dec 30;205(3):1770–1775. doi: 10.1006/bbrc.1994.2874. [DOI] [PubMed] [Google Scholar]
  12. Kuroda S., Tokunaga C., Kiyohara Y., Higuchi O., Konishi H., Mizuno K., Gill G. N., Kikkawa U. Protein-protein interaction of zinc finger LIM domains with protein kinase C. J Biol Chem. 1996 Dec 6;271(49):31029–31032. doi: 10.1074/jbc.271.49.31029. [DOI] [PubMed] [Google Scholar]
  13. Martiny-Baron G., Kazanietz M. G., Mischak H., Blumberg P. M., Kochs G., Hug H., Marmé D., Schächtele C. Selective inhibition of protein kinase C isozymes by the indolocarbazole Gö 6976. J Biol Chem. 1993 May 5;268(13):9194–9197. [PubMed] [Google Scholar]
  14. Mendez R., Kollmorgen G., White M. F., Rhoads R. E. Requirement of protein kinase C zeta for stimulation of protein synthesis by insulin. Mol Cell Biol. 1997 Sep;17(9):5184–5192. doi: 10.1128/mcb.17.9.5184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Palmer R. H., Dekker L. V., Woscholski R., Le Good J. A., Gigg R., Parker P. J. Activation of PRK1 by phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. A comparison with protein kinase C isotypes. J Biol Chem. 1995 Sep 22;270(38):22412–22416. doi: 10.1074/jbc.270.38.22412. [DOI] [PubMed] [Google Scholar]
  16. Quon M. J., Butte A. J., Zarnowski M. J., Sesti G., Cushman S. W., Taylor S. I. Insulin receptor substrate 1 mediates the stimulatory effect of insulin on GLUT4 translocation in transfected rat adipose cells. J Biol Chem. 1994 Nov 11;269(45):27920–27924. [PubMed] [Google Scholar]
  17. Quon M. J., Chen H., Ing B. L., Liu M. L., Zarnowski M. J., Yonezawa K., Kasuga M., Cushman S. W., Taylor S. I. Roles of 1-phosphatidylinositol 3-kinase and ras in regulating translocation of GLUT4 in transfected rat adipose cells. Mol Cell Biol. 1995 Oct;15(10):5403–5411. doi: 10.1128/mcb.15.10.5403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Quon M. J., Guerre-Millo M., Zarnowski M. J., Butte A. J., Em M., Cushman S. W., Taylor S. I. Tyrosine kinase-deficient mutant human insulin receptors (Met1153-->Ile) overexpressed in transfected rat adipose cells fail to mediate translocation of epitope-tagged GLUT4. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5587–5591. doi: 10.1073/pnas.91.12.5587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Quon M. J., Zarnowski M. J., Guerre-Millo M., de la Luz Sierra M., Taylor S. I., Cushman S. W. Transfection of DNA into isolated rat adipose cells by electroporation: evaluation of promoter activity in transfected adipose cells which are highly responsive to insulin after one day in culture. Biochem Biophys Res Commun. 1993 Jul 15;194(1):338–346. doi: 10.1006/bbrc.1993.1825. [DOI] [PubMed] [Google Scholar]
  20. Standaert M. L., Avignon A., Yamada K., Bandyopadhyay G., Farese R. V. The phosphatidylinositol 3-kinase inhibitor, wortmannin, inhibits insulin-induced activation of phosphatidylcholine hydrolysis and associated protein kinase C translocation in rat adipocytes. Biochem J. 1996 Feb 1;313(Pt 3):1039–1046. doi: 10.1042/bj3131039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Standaert M. L., Galloway L., Karnam P., Bandyopadhyay G., Moscat J., Farese R. V. Protein kinase C-zeta as a downstream effector of phosphatidylinositol 3-kinase during insulin stimulation in rat adipocytes. Potential role in glucose transport. J Biol Chem. 1997 Nov 28;272(48):30075–30082. doi: 10.1074/jbc.272.48.30075. [DOI] [PubMed] [Google Scholar]
  22. Standaert M., Bandyopadhyay G., Galloway L., Ono Y., Mukai H., Farese R. Comparative effects of GTPgammaS and insulin on the activation of Rho, phosphatidylinositol 3-kinase, and protein kinase N in rat adipocytes. Relationship to glucose transport. J Biol Chem. 1998 Mar 27;273(13):7470–7477. doi: 10.1074/jbc.273.13.7470. [DOI] [PubMed] [Google Scholar]
  23. Stokoe D., Stephens L. R., Copeland T., Gaffney P. R., Reese C. B., Painter G. F., Holmes A. B., McCormick F., Hawkins P. T. Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. Science. 1997 Jul 25;277(5325):567–570. doi: 10.1126/science.277.5325.567. [DOI] [PubMed] [Google Scholar]
  24. Tanti J. F., Grillo S., Grémeaux T., Coffer P. J., Van Obberghen E., Le Marchand-Brustel Y. Potential role of protein kinase B in glucose transporter 4 translocation in adipocytes. Endocrinology. 1997 May;138(5):2005–2010. doi: 10.1210/endo.138.5.5136. [DOI] [PubMed] [Google Scholar]
  25. Toker A., Meyer M., Reddy K. K., Falck J. R., Aneja R., Aneja S., Parra A., Burns D. J., Ballas L. M., Cantley L. C. Activation of protein kinase C family members by the novel polyphosphoinositides PtdIns-3,4-P2 and PtdIns-3,4,5-P3. J Biol Chem. 1994 Dec 23;269(51):32358–32367. [PubMed] [Google Scholar]
  26. Zhou L., Chen H., Lin C. H., Cong L. N., McGibbon M. A., Sciacchitano S., Lesniak M. A., Quon M. J., Taylor S. I. Insulin receptor substrate-2 (IRS-2) can mediate the action of insulin to stimulate translocation of GLUT4 to the cell surface in rat adipose cells. J Biol Chem. 1997 Nov 21;272(47):29829–29833. doi: 10.1074/jbc.272.47.29829. [DOI] [PubMed] [Google Scholar]