title: Tissue specific differences in the insulin receptor kinase activated in vitro and in vivo.
abstract: We have recently described structural differences between insulin receptors isolated from rat skeletal muscle and liver. In this report we compared their intrinsic kinase activity and their precipitability with antiphosphotyrosine and polyclonal anti-beta-subunit antibodies before and after stimulation by insulin in vitro or in vivo. Liver derived receptors incubated with insulin showed 40-50% less autophosphorylation and exogenous substrate tyrosine kinase activity per insulin binding site than those from muscle, as well as a 50% reduction in the proportion of antiphosphotyrosine precipitable receptors. After tyrosine kinase was maximally activated by iv insulin injection (in vivo), antiphosphotyrosine antibodies precipitated 60% and 38% of insulin receptors from muscle and liver, respectively. Addition of insulin in vitro to in vivo activated receptors increased the proportion of antiphosphotyrosine antibody-precipitable receptors in both tissues but increased the tyrosine kinase activity only in liver-derived receptors, indicating that most activatable insulin receptors reside on the plasmalemma in muscle whereas a significant proportion (35%) of liver receptors are not accessible to insulin in vivo. No tissue specific differences were apparent in the interaction of three site specific anti-beta-subunit antibodies with the receptors.
  
  
  CONCLUSIONS
  1) The intrinsic kinase activity per insulin binding site is less in liver than in muscle. This reflects in part the greater proportion of insulin receptors from liver which do not autophosphorylate on tyrosine upon insulin binding. 2) Some insulin receptors can be phosphorylated on tyrosine in vitro without concomitant exogenous tyrosine kinase activation.
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston 29425.
authors.forename: C F
authors.initials: CF
authors.lastname: Burant
authors.forename: M K
authors.initials: MK
authors.lastname: Treutelaar
authors.forename: M G
authors.initials: MG
authors.lastname: Buse
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D006657:Histones / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D009132:Muscles / Q000201:enzymology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism
chemical_list: D006657:Histones; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin