Functional trans-inactivation of insulin receptor kinase by growth-inhibitory angiotensin II AT2 receptor

被引:51
作者
Elbaz, N [1 ]
Bedecs, K [1 ]
Masson, M [1 ]
Sutren, M [1 ]
Strosberg, AD [1 ]
Nahmias, C [1 ]
机构
[1] CNRS, ICGM, UPR 1415, F-75014 Paris, France
关键词
D O I
10.1210/me.14.6.795
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The present study demonstrates negative intracellular cross-talk between angiotensin II type 2 (AT(2)) and insulin receptors. AT(2) receptor stimulation leads to inhibition of insulin-induced extracellular signal-regulated protein kinase (ERK2) activity and cell proliferation in transfected Chinese hamster ovary (CHO-hAT(2)) cells. We show that AT(2) receptor interferes at the initial step of insulin signaling cascade, by impairing tyrosine phosphorylation of the insulin receptor (IR) beta-chain. AT(2)-mediated inhibition of IR phosphorylation is insensitive to pertussis toxin and is also detected in neuroblastoma N1E-115 and pancreatic acinar AR42J cells that express endogenous receptors. We present evidence that AT(2) receptor inhibits the autophosphorylating tyrosine kinase activity of IR, with no significant effect on insulin binding properties. AT(2)-mediated inactivation of IR does not mainly involve tyrosine dephosphorylation by vanadate-sensitive tyrosine phosphatases nor serine/threonine phosphorylation by protein kinase C. As a consequence of IR inactivation, AT(2) receptor inhibits tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and signal-regulatory protein (SIRP alpha 1) and prevents subsequent association of both IRS-1 and SIRP alpha 1 with Src homology 2 (SH2)-containing tyrosine phosphatase SHP-2. Our results thus demonstrate functional trans-inactivation of IR kinase by G protein-coupled AT(2) receptor, illustrating a novel mode of negative communication between two families of membrane receptors.
引用
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页码:795 / 804
页数:10
相关论文
共 74 条
[1]   Expression of the AT2 receptor developmentally programs extracellular signal-regulated kinase activity and influences fetal vascular growth [J].
Akishita, M ;
Ito, M ;
Lehtonen, YA ;
Daviet, L ;
Dzau, VJ ;
Horiuchi, M .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (01) :63-71
[2]   Angiotensin II stimulates tyrosine phosphorylation and activation of insulin receptor substrate 1 and protein-tyrosine phosphatase 1D in vascular smooth muscle cells [J].
Ali, MS ;
Schieffer, B ;
Delafontaine, P ;
Bernstein, KE ;
Ling, BN ;
Marrero, MB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (19) :12373-12379
[3]   Angiotensin II type 2 receptor blockade amplifies the early signals of cardiac growth response to angiotensin II in hypertrophied hearts [J].
Bartunek, J ;
Weinberg, EO ;
Tajima, M ;
Rohrbach, S ;
Lorell, BH .
CIRCULATION, 1999, 99 (01) :22-25
[4]   Angiotensin II type 2 receptors mediate inhibition of mitogen-activated protein kinase cascade and functional activation of SHP-1 tyrosine phosphatase [J].
Bedecs, K ;
Elbaz, N ;
Sutren, M ;
Masson, M ;
Susini, C ;
Strosberg, AD ;
Nahmias, C .
BIOCHEMICAL JOURNAL, 1997, 325 :449-454
[5]  
Berk BC, 1999, J AM SOC NEPHROL, V10, pS62
[6]   Protein kinase C isoforms beta 1 and beta 2 inhibit the tyrosine kinase activity of the insulin receptor [J].
Bossenmaier, B ;
Mosthaf, L ;
Mischak, H ;
Ullrich, A ;
Haring, HU .
DIABETOLOGIA, 1997, 40 (07) :863-866
[7]   THE ANGIOTENSIN-AT2 RECEPTOR STIMULATES PROTEIN TYROSINE PHOSPHATASE-ACTIVITY AND MEDIATES INHIBITION OF PARTICULATE GUANYLATE-CYCLASE [J].
BOTTARI, SP ;
KING, IN ;
REICHLIN, S ;
DAHLSTROEM, I ;
LYDON, N ;
DEGASPARO, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1992, 183 (01) :206-211
[8]   sst2 somatostatin receptor mediates negative regulation of insulin receptor signaling through the tyrosine phosphatase SHP-1 [J].
Bousquet, C ;
Delesque, N ;
Lopez, F ;
Saint-Laurent, N ;
Estève, JP ;
Bedecs, K ;
Buscail, L ;
Vaysse, N ;
Susini, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (12) :7099-7106
[9]  
BRECHLER V, 1994, RECEPTOR CHANNEL, V2, P89
[10]   A G-PROTEIN IS INVOLVED IN THE ANGIOTENSIN AT(2) RECEPTOR INHIBITION OF THE T-TYPE CALCIUM CURRENT IN NON-DIFFERENTIATED NG108-15 CELLS [J].
BUISSON, B ;
LAFLAMME, L ;
BOTTARI, SP ;
DEGASPARO, M ;
GALLOPAYET, N ;
PAYET, MD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (04) :1670-1674