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Biochem J. Mar 15, 2002; 362(Pt 3): 665–674.
PMCID: PMC1222431

Sorbitol activates atypical protein kinase C and GLUT4 glucose transporter translocation/glucose transport through proline-rich tyrosine kinase-2, the extracellular signal-regulated kinase pathway and phospholipase D.

Abstract

Sorbitol, "osmotic stress", stimulates GLUT4 glucose transporter translocation to the plasma membrane and glucose transport by a phosphatidylinositol (PI) 3-kinase-independent mechanism that reportedly involves non-receptor proline-rich tyrosine kinase-2 (PYK2) but subsequent events are obscure. In the present study, we found that extracellular signal-regulated kinase (ERK) pathway components, growth-factor-receptor-bound-2 protein, son of sevenless (SOS), RAS, RAF and mitogen-activated protein (MAP) kinase/ERK kinase, MEK(-1), operating downstream of PYK2, were required for sorbitol-stimulated GLUT4 translocation/glucose transport in rat adipocytes, L6 myotubes and 3T3/L1 adipocytes. Furthermore, sorbitol activated atypical protein kinase C (aPKC) through a similar mechanism depending on the PYK2/ERK pathway, independent of PI 3-kinase and its downstream effector, 3-phosphoinositide-dependent protein kinase-1 (PDK-1). Like PYK2/ERK pathway components, aPKCs were required for sorbitol-stimulated GLUT4 translocation/glucose transport. Interestingly, sorbitol stimulated increases in phospholipase D (PLD) activity and generation of phosphatidic acid (PA), which directly activated aPKCs. As with aPKCs and glucose transport, sorbitol-stimulated PLD activity was dependent on the ERK pathway. Moreover, PLD-generated PA was required for sorbitol-induced activation of aPKCs and GLUT4 translocation/glucose transport. Our findings suggest that sorbitol sequentially activates PYK2, the ERK pathway and PLD, thereby increasing PA, which activates aPKCs and GLUT4 translocation. This mechanism contrasts with that of insulin, which primarily uses PI 3-kinase, D3-PO(4) polyphosphoinositides and PDK-1 to activate aPKCs.

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Selected References

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  • Chen D, Elmendorf JS, Olson AL, Li X, Earp HS, Pessin JE. Osmotic shock stimulates GLUT4 translocation in 3T3L1 adipocytes by a novel tyrosine kinase pathway. J Biol Chem. 1997 Oct 24;272(43):27401–27410. [PubMed]
  • Trudeau JD, Dutz JP, Arany E, Hill DJ, Fieldus WE, Finegood DT. Neonatal beta-cell apoptosis: a trigger for autoimmune diabetes? Diabetes. 2000 Jan;49(1):1–7. [PubMed]
  • Bandyopadhyay G, Standaert ML, Zhao L, Yu B, Avignon A, Galloway L, Karnam P, Moscat J, Farese RV. 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. [PubMed]
  • Standaert ML, Galloway L, Karnam P, Bandyopadhyay G, Moscat J, Farese RV. 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. [PubMed]
  • Bandyopadhyay G, Standaert ML, Galloway L, Moscat J, Farese RV. 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. [PubMed]
  • Kotani K, Ogawa W, Matsumoto M, Kitamura T, Sakaue H, Hino Y, Miyake K, Sano W, Akimoto K, Ohno S, et al. Requirement of atypical protein kinase clambda for insulin stimulation of glucose uptake but not for Akt activation in 3T3-L1 adipocytes. Mol Cell Biol. 1998 Dec;18(12):6971–6982. [PMC free article] [PubMed]
  • Kohn AD, Summers SA, Birnbaum MJ, Roth RA. Expression of a constitutively active Akt Ser/Thr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation. J Biol Chem. 1996 Dec 6;271(49):31372–31378. [PubMed]
  • Tanti JF, Grillo S, Grémeaux T, Coffer PJ, 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. [PubMed]
  • Wang Q, Somwar R, Bilan PJ, Liu Z, Jin J, Woodgett JR, Klip A. Protein kinase B/Akt participates in GLUT4 translocation by insulin in L6 myoblasts. Mol Cell Biol. 1999 Jun;19(6):4008–4018. [PMC free article] [PubMed]
  • Hill MM, Clark SF, Tucker DF, Birnbaum MJ, James DE, Macaulay SL. A role for protein kinase Bbeta/Akt2 in insulin-stimulated GLUT4 translocation in adipocytes. Mol Cell Biol. 1999 Nov;19(11):7771–7781. [PMC free article] [PubMed]
  • Blaukat A, Ivankovic-Dikic I, Grönroos E, Dolfi F, Tokiwa G, Vuori K, Dikic I. Adaptor proteins Grb2 and Crk couple Pyk2 with activation of specific mitogen-activated protein kinase cascades. J Biol Chem. 1999 May 21;274(21):14893–14901. [PubMed]
  • Kozma L, Baltensperger K, Klarlund J, Porras A, Santos E, Czech MP. The ras signaling pathway mimics insulin action on glucose transporter translocation. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4460–4464. [PMC free article] [PubMed]
  • Quon MJ, Chen H, Ing BL, Liu ML, Zarnowski MJ, Yonezawa K, Kasuga M, Cushman SW, Taylor SI. 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. [PMC free article] [PubMed]
  • Limatola C, Schaap D, Moolenaar WH, van Blitterswijk WJ. Phosphatidic acid activation of protein kinase C-zeta overexpressed in COS cells: comparison with other protein kinase C isotypes and other acidic lipids. Biochem J. 1994 Dec 15;304(Pt 3):1001–1008. [PMC free article] [PubMed]
  • Limatola C, Barabino B, Nista A, Santoni A. Interleukin 1-beta-induced protein kinase C-zeta activation is mimicked by exogenous phospholipase D. Biochem J. 1997 Jan 15;321(Pt 2):497–501. [PMC free article] [PubMed]
  • Standaert ML, Bandyopadhyay G, Perez L, Price D, Galloway L, Poklepovic A, Sajan MP, Cenni V, Sirri A, Moscat J, et al. Insulin activates protein kinases C-zeta and C-lambda by an autophosphorylation-dependent mechanism and stimulates their translocation to GLUT4 vesicles and other membrane fractions in rat adipocytes. J Biol Chem. 1999 Sep 3;274(36):25308–25316. [PubMed]
  • Bandyopadhyay G, Standaert ML, Kikkawa U, Ono Y, Moscat J, Farese RV. 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. Biochem J. 1999 Feb 1;337(Pt 3):461–470. [PMC free article] [PubMed]
  • Bandyopadhyay G, Sajan MP, Kanoh Y, Standaert ML, Burke TR, Jr, Quon MJ, Reed BC, Dikic I, Noel LE, Newgard CB, et al. Glucose activates mitogen-activated protein kinase (extracellular signal-regulated kinase) through proline-rich tyrosine kinase-2 and the Glut1 glucose transporter. J Biol Chem. 2000 Dec 29;275(52):40817–40826. [PubMed]
  • Bandyopadhyay G, Standaert ML, Sajan MP, Karnitz LM, Cong L, Quon MJ, Farese RV. Dependence of insulin-stimulated glucose transporter 4 translocation on 3-phosphoinositide-dependent protein kinase-1 and its target threonine-410 in the activation loop of protein kinase C-zeta. Mol Endocrinol. 1999 Oct;13(10):1766–1772. [PubMed]
  • Sajan MP, Standaert ML, Bandyopadhyay G, Quon MJ, Burke TR, Jr, Farese RV. Protein kinase C-zeta and phosphoinositide-dependent protein kinase-1 are required for insulin-induced activation of ERK in rat adipocytes. J Biol Chem. 1999 Oct 22;274(43):30495–30500. [PubMed]
  • Bandyopadhyay G, Kanoh Y, Sajan MP, Standaert ML, Farese RV. Effects of adenoviral gene transfer of wild-type, constitutively active, and kinase-defective protein kinase C-lambda on insulin-stimulated glucose transport in L6 myotubes. Endocrinology. 2000 Nov;141(11):4120–4127. [PubMed]
  • Standaert ML, Avignon A, Yamada K, Bandyopadhyay G, Farese RV. 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. [PMC free article] [PubMed]
  • Emoto M, Klarlund JK, Waters SB, Hu V, Buxton JM, Chawla A, Czech MP. A role for phospholipase D in GLUT4 glucose transporter translocation. J Biol Chem. 2000 Mar 10;275(10):7144–7151. [PubMed]
  • Djerdjouri B, Lenoir M, Giroud JP, Périanin A. Contribution of mitogen-activated protein kinase to stimulation of phospholipase D by the chemotactic peptide fMet-Leu-Phe in human neutrophils. Biochem Biophys Res Commun. 1999 Oct 22;264(2):371–375. [PubMed]
  • Reinhold SL, Prescott SM, Zimmerman GA, McIntyre TM. Activation of human neutrophil phospholipase D by three separable mechanisms. FASEB J. 1990 Feb 1;4(2):208–214. [PubMed]
  • Kessels GC, Krause KH, Verhoeven AJ. Protein kinase C activity is not involved in N-formylmethionyl-leucyl-phenylalanine-induced phospholipase D activation in human neutrophils, but is essential for concomitant NADPH oxidase activation: studies with a staurosporine analogue with improved selectivity for protein kinase C. Biochem J. 1993 Jun 15;292(Pt 3):781–785. [PMC free article] [PubMed]
  • Lopez I, Burns DJ, Lambeth JD. Regulation of phospholipase D by protein kinase C in human neutrophils. Conventional isoforms of protein kinase C phosphorylate a phospholipase D-related component in the plasma membrane. J Biol Chem. 1995 Aug 18;270(33):19465–19472. [PubMed]
  • Jiang H, Lu Z, Luo JQ, Wolfman A, Foster DA. Ras mediates the activation of phospholipase D by v-Src. J Biol Chem. 1995 Mar 17;270(11):6006–6009. [PubMed]
  • Bandyopadhyay G, Sajan MP, Kanoh Y, Standaert ML, Quon MJ, Reed BC, Dikic I, Farese RV. Glucose activates protein kinase C-zeta /lambda through proline-rich tyrosine kinase-2, extracellular signal-regulated kinase, and phospholipase D: a novel mechanism for activating glucose transporter translocation. J Biol Chem. 2001 Sep 21;276(38):35537–35545. [PubMed]

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