Najjar S M, Blakesley V A, Li Calzi S, Kato H, LeRoith D, Choice C V
Department of Pharmacology and Therapeutics, Medical College of Ohio, Toledo 43614, USA.
Biochemistry. 1997 Jun 3;36(22):6827-34. doi: 10.1021/bi962634h.
pp 120, a plasma membrane glycoprotein expressed by hepatocytes, is a substrate of the insulin receptor tyrosine kinase. Since insulin-like growth factor-1 (IGF-1) and insulin receptors are structurally homologous, we investigated whether pp120 is also a substrate of the IGF-1 receptor tyrosine kinase. IGF-1 receptor failed to phosphorylate pp120 in response to IGF-1 in stably transfected NIH 3T3 fibroblasts. However, replacement of the C-terminal domain of the beta-subunit of the IGF-1 receptor with the corresponding fragment in the insulin receptor restored ligand-stimulated pp120 phosphorylation, suggesting that this domain plays a regulatory role in pp120 phosphorylation. Since pp120 is the first identified substrate specific for the insulin vis-à-vis the IGF-1 receptor tyrosine kinase, the pp120 signaling pathway may constitute a novel mechanism for the distinct cellular effects of insulin and IGF-1, the former being principally involved in metabolism, and the latter in mitogenesis.
pp120是一种由肝细胞表达的质膜糖蛋白，是胰岛素受体酪氨酸激酶的底物。由于胰岛素样生长因子-1（IGF-1）和胰岛素受体在结构上具有同源性，我们研究了pp120是否也是IGF-1受体酪氨酸激酶的底物。在稳定转染的NIH 3T3成纤维细胞中，IGF-1受体在IGF-1刺激下未能使pp120磷酸化。然而，用胰岛素受体中的相应片段替换IGF-1受体β亚基的C末端结构域可恢复配体刺激的pp120磷酸化，这表明该结构域在pp120磷酸化中起调节作用。由于pp120是第一个被确定的相对于IGF-1受体酪氨酸激酶而言对胰岛素具有特异性的底物，pp120信号通路可能构成胰岛素和IGF-1不同细胞效应的一种新机制，前者主要参与代谢，后者主要参与有丝分裂。
