DIFFERENTIAL PHOSPHORYLATION OF PP120 BY INSULIN AND INSULIN-LIKE GROWTH-FACTOR-I RECEPTORS - ROLE FOR THE C-TERMINAL DOMAIN OF THE BETA-SUBUNIT

pp120, a plasma membrane glycoprotein expressed by hepatocytes, is a s ubstrate of the insulin receptor tyrosine kinase, Since insulin-like g rowth factor-1 (IGF-1) and insulin receptors are structurally homologo us, we investigated whether pp120 is also a substrate of the IGF-1 rec eptor tyrosine kinase. ICF-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 rest ored ligand-stimulated pp120 phosphorylation, suggesting that this dom ain plays a regulatory role in pp120 phosphorylation. Since pp120 is t he first identified substrate specific for the insulin vis-a vis the I GF-1 receptor tyrosine kinase, the pp120 signaling pathway may constit ute a novel mechanism for the distinct cellular effects of insulin and IGF-1, the former being principally involved in metabolism, and the l atter in mitogenesis.