Differential phosphorylation of pp120 by insulin and insulin-like growth factor-1 receptors: role for the C-terminal domain of the beta-subunit.
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.
Najjar
S M
SM
Department of Pharmacology and Therapeutics, Medical College of Ohio, Toledo 43614, USA. snajjar@opus.mco.edu
Blakesley
V A
VA
Li Calzi
S
S
Kato
H
H
LeRoith
D
D
Choice
C V
CV
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
D002352:Carrier Proteins; D006913:Hydroxysteroid Dehydrogenases; D007334:Insulin-Like Growth Factor I; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D019000:Phosphotyrosine; D020794:Receptor Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D011994:Recombinant Proteins; C037643:bile acid binding proteins; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)