Cellular signaling by the insulin receptor.
Cellular signaling by insulin is initiated by specific membrane receptors that have been characterized as large multimeric disulfide-linked protein complexes with a minimal subunit structure of (beta-S-S-alpha)-S-S-(alpha-S-S-beta), where the alpha- and beta-subunits are about 125,000 and 90,000 daltons, respectively. The disulfides in this structure are of two classes based on their differential sensitivity to reductants (Massague, J., and Czech, M. P., J. Biol. Chem. 1982; 257:6729-35). An important recent discovery is that the insulin receptor, either in crude detergent extracts or after purification by affinity chromatography, is associated with insulin-activatable tyrosine phosphokinase activity and is itself autophosphorylated (Kasuga, M., et al., Proc. Natl. Acad. Sci. USA 1983; 80:2137-41). We demonstrate here that insulin receptor kinase activity is readily monitored while the receptor is absorbed onto insulin-agarose, using [gamma-32]ATP and histone as substrate. Phosphorylation of histone and the receptor beta-subunit on tyrosine residues is dependent on time, temperature, and Mn2+ in this system. The immobilized insulin receptor kinase is activated by prior phosphorylation with ATP, indicating that the autophosphorylation plays an important role in regulating receptor kinase activity. That the insulin receptor tyrosine kinase activity may be involved in initiating the mechanism of insulin action is currently an attractive hypothesis. A second working model of insulin action proposes that one or more soluble factors are released into the cell in response to insulin as suggested by studies using muscle and fat cell extracts.(ABSTRACT TRUNCATED AT 250 WORDS)
D000273:Adipose Tissue / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin / Q000187:drug effects / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism
D000596:Amino Acids; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin