Insulin-like growth factor receptor-1 stimulates phosphorylation of the beta(2)-adrenergic receptor in vivo on sites distinct from those phosphorylated in response to insulin

被引:52
作者
Karoor, V [1 ]
Malbon, CC [1 ]
机构
[1] SUNY STONY BROOK, SCH MED, DIABET & METAB DIS RES CTR, DEPT MOL PHARMACOL, STONY BROOK, NY 11794 USA
关键词
D O I
10.1074/jbc.271.46.29347
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
G-protein-linked receptors have been shown to be substrates for growth factor receptors with intrinsic tyrosine kinase activity typified by the ability of insulin to both phosphorylate tyrosyl residues in the C terminus of and to counter-regulate the action of the beta(2)-adrenergic receptor (Karoor, V., Baltensperger, K., Paul, H., Czech, M. P., and Malbon, C, C, (1995) J. Biol. Chem, 270, 25305-25308). Insulin-like growth factor-1 (IGF-1), another member of the growth factor family operating via receptors with intrinsic tyrosine kinase, is shown in the present work to stimulate in vivo the phosphorylation of the beta(2)-adrenergic receptor. Analysis of tryptic digests prepared from phosphorylated beta(2)-adrenergic receptors of IGF-1-treated, metabolically labeled smooth muscle cells was performed using reversed-phase high performance liquid chromatography, two-dimensional peptide mapping, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The results of these separate analyses reveal that IGF-1 stimulates phosphorylation predominantly on tyrosyl residues Y132/141 of the second intracellular loop of the beta(2)-adrenergic receptor rather than the C-terminal region targeted by the activated insulin receptor (Y350/354, Y364), although both growth factors block beta-adrenergic agonist action. These data demonstrate selective phosphorylation of a G-protein-linked receptor by receptor tyrosine kinases for insulin and IGF-1 mapping to spatially distinct regions of this heptihelical membrane receptor.
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页码:29347 / 29352
页数:6
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