Tissue Specific Differences in the Insulin Receptor Kinase Activated in Vitro and in Vivo*
- 1 February 1988
- journal article
- research article
- Published by The Endocrine Society in Endocrinology
- Vol. 122 (2) , 427-437
- https://doi.org/10.1210/endo-122-2-427
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.This publication has 23 references indexed in Scilit:
- Characterization of affinity-purified insulin receptor/kinase. Effects of dithiothreitol on receptor/kinase function.Journal of Biological Chemistry, 1986
- Antibodies to deduced sequences of the insulin receptor distinguish conserved and nonconserved regions in the IGF-I receptor.Journal of Biological Chemistry, 1986
- Insulin action is blocked by a monoclonal antibody that inhibits the insulin receptor kinase.Proceedings of the National Academy of Sciences, 1986
- Diabetes-induced functional and structural changes in insulin receptors from rat skeletal muscle.Journal of Clinical Investigation, 1986
- An antipeptide antibody that specifically inhibits insulin receptor autophosphorylation and protein kinase activity.Proceedings of the National Academy of Sciences, 1985
- Insulin receptor kinase activity in rat liver. Regulation by fasting and high carbohydrate feeding.Journal of Biological Chemistry, 1985
- Differences in the sites of phosphorylation of the insulin receptor in vivo and in vitro.Journal of Biological Chemistry, 1985
- Decreased autophosphorylation of the insulin receptor-kinase in streptozotocin-diabetic rats.Journal of Biological Chemistry, 1984
- ON THE MECHANISM OF LIGAND-INDUCED DOWN-REGULATION OF INSULIN-RECEPTOR LEVEL IN THE LIVER-CELL1981
- Intracellular polypeptide hormone receptors. The demonstration of specific binding sites for insulin and human growth hormone in Golgi fractions isolated from the liver of female rats.Journal of Biological Chemistry, 1978