INSULIN-RECEPTOR SUBSTRATE-1 IS PHOSPHORYLATED BY THE SERINE KINASE-ACTIVITY OF PHOSPHATIDYLINOSITOL 3-KINASE

被引：82

作者：

TANTI, JF

GREMEAUX, T

VANOBBERGHEN, E

LEMARCHANDBRUSTEL, Y

机构：

[1] Inst National Sante Recherche Medic, INSERM U 145, Faculte de Medecine, 06107 Nice Cedex 02, Avenue de Valombrose

来源：

BIOCHEMICAL JOURNAL | 1994年 / 304卷

关键词：

D O I：

10.1042/bj3040017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Insulin receptor substrate (IRS) 1, which is tyrosine phosphorylated in response to insulin, presents multiple serine/threonine phosphorylation sites. To search for a serine kinase activity towards IRS 1, immunoprecipitates from basal or stimulated 3T3-L1 adipocytes were used in an in vitro kinase assay. When IRS 1 was isolated from insulin-treated cells, serine phosphorylation of IRS 1 occurred, which we attribute to the kinase activity of the phosphatidylinositol 3-kinase (PI3-kinase). Importantly, in an in vitro reconstitution assay, an excess of the PI3-kinase subunit prevents this phosphorylation. Together, our results suggest that following insulin stimulation, PI3-kinase associates with IRS 1, allowing for its serine phosphorylation. This phosphorylation event could play a role in the modulation of insulin signalling.

引用

页码：17 / 21

页数：5

共 34 条

[1] PHOSPHATIDYLINOSITOL 3'-KINASE IS ACTIVATED BY ASSOCIATION WITH IRS-1 DURING INSULIN STIMULATION [J].

BACKER, JM ;

MYERS, MG ;

SHOELSON, SE ;

CHIN, DJ ;

SUN, XJ ;

MIRALPEIX, M ;

HU, P ;

MARGOLIS, B ;

SKOLNIK, EY ;

SCHLESSINGER, J ;

WHITE, MF .

EMBO JOURNAL, 1992, 11 (09) :3469-3479

[2]

BACKER JM, 1993, J BIOL CHEM, V268, P8204

[3] PROTEIN-KINASE-C DIRECTLY PHOSPHORYLATES THE INSULIN-RECEPTOR INVITRO AND REDUCES ITS PROTEIN-TYROSINE KINASE-ACTIVITY [J].

BOLLAG, GE ;

ROTH, RA ;

BEAUDOIN, J ;

MOCHLYROSEN, D ;

KOSHLAND, DE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (16) :5822-5824

[4] CAMP ANTAGONIZES P21(RAS)-DIRECTED ACTIVATION OF EXTRACELLULAR SIGNAL-REGULATED KINASE-2 AND PHOSPHORYLATION OF MSOS NUCLEOTIDE EXCHANGE FACTOR [J].

BURGERING, BMT ;

PRONK, GJ ;

VANWEEREN, PC ;

CHARDIN, P ;

BOS, JL .

EMBO JOURNAL, 1993, 12 (11) :4211-4220

[5] A TIGHTLY ASSOCIATED SERINE THREONINE PROTEIN-KINASE REGULATES PHOSPHOINOSITIDE 3-KINASE ACTIVITY [J].

CARPENTER, CL ;

AUGER, KR ;

DUCKWORTH, BC ;

HOU, WM ;

SCHAFFHAUSEN, B ;

CANTLEY, LC .

MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (03) :1657-1665

[6] INHIBITION OF THE TRANSLOCATION OF GLUT1 AND GLUT4 IN 3T3-L1 CELLS BY THE PHOSPHATIDYLINOSITOL 3-KINASE INHIBITOR, WORTMANNIN [J].

CLARKE, JF ;

YOUNG, PW ;

YONEZAWA, K ;

KASUGA, M ;

HOLMAN, GD .

BIOCHEMICAL JOURNAL, 1994, 300 :631-635

[7] PI-3-KINASE IS A DUAL-SPECIFICITY ENZYME - AUTOREGULATION BY AN INTRINSIC PROTEIN-SERINE KINASE-ACTIVITY [J].

DHAND, R ;

HILES, I ;

PANAYOTOU, G ;

ROCHE, S ;

FRY, MJ ;

GOUT, I ;

TOTTY, NF ;

TRUONG, O ;

VICENDO, P ;

YONEZAWA, K ;

KASUGA, M ;

COURTNEIDGE, SA ;

WATERFIELD, MD .

EMBO JOURNAL, 1994, 13 (03) :522-533

[8] CDNA CLONING OF A NOVEL 85KD PROTEIN THAT HAS SH2 DOMAINS AND REGULATES BINDING OF PI3-KINASE TO THE PDGF BETA-RECEPTOR [J].

ESCOBEDO, JA ;

NAVANKASATTUSAS, S ;

KAVANAUGH, WM ;

MILFAY, D ;

FRIED, VA ;

WILLIAMS, LT .

CELL, 1991, 65 (01) :75-82

[9]

GIORGETTI S, 1993, J BIOL CHEM, V268, P7358

[10] 1-PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY IS REQUIRED FOR INSULIN-STIMULATED GLUCOSE-TRANSPORT BUT NOT FOR RAS ACTIVATION IN CHO CELLS [J].

HARA, K ;

YONEZAWA, K ;

SAKAUE, H ;

ANDO, A ;

KOTANI, K ;

KITAMURA, T ;

KITAMURA, Y ;

UEDA, H ;

STEPHENS, L ;

JACKSON, TR ;

HAWKINS, PT ;

DHAND, R ;

CLARK, AE ;

HOLMAN, GD ;

WATERFIELD, MD ;

KASUGA, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (16) :7415-7419

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