Karoor V, Baltensperger K, Paul H, Czech M P, Malbon C C
Department of Molecular Pharmacology, State University of New York, Stony Brook 11794-8651, USA.
J Biol Chem. 1995 Oct 27;270(43):25305-8. doi: 10.1074/jbc.270.43.25305.
Insulin stimulates a loss of function and increased phosphotyrosine content of the beta 2-adrenergic receptor in intact cells, raising the possibility that the beta 2-receptor itself is a substrate for the insulin receptor tyrosine kinase. Phosphorylation of synthetic peptides corresponding to cytoplasmic domains of the beta 2-adrenergic receptor by the insulin receptor in vitro and peptide mapping of the beta 2-adrenergic receptor phosphorylated in vivo in cells stimulated by insulin reveal tyrosyl residues 350/354 and 364 in the cytoplasmic, C-terminal region of the beta 2-adrenergic receptor as primary targets. Mutation of tyrosyl residues 350, 354 (double mutation) to phenylalanine abolishes the ability of insulin to counterregulate beta-agonist stimulation of cyclic AMP accumulation. Phenylalanine substitution of tyrosyl reside 364, in contrast, abolishes beta-adrenergic stimulation itself.
胰岛素可刺激完整细胞中β2 - 肾上腺素能受体功能丧失并增加其磷酸酪氨酸含量，这增加了β2 - 受体本身是胰岛素受体酪氨酸激酶底物的可能性。体外胰岛素受体对与β2 - 肾上腺素能受体胞质结构域相对应的合成肽进行磷酸化，以及对胰岛素刺激的细胞中体内磷酸化的β2 - 肾上腺素能受体进行肽图谱分析，结果显示β2 - 肾上腺素能受体胞质C末端区域的酪氨酸残基350/354和364是主要靶点。将酪氨酸残基350、354突变为苯丙氨酸（双突变）会消除胰岛素对β - 激动剂刺激环磷酸腺苷积累的反向调节能力。相比之下，将酪氨酸残基364替换为苯丙氨酸会消除β - 肾上腺素能刺激本身。
