Insulin stimulates the tyrosine dephosphorylation of docking protein p130cas (Crk-associated substrate), promoting the switch of the adaptor protein crk from p130cas to newly phosphorylated insulin receptor substrate-1. 1998

A Sorokin, and E Reed
Department of Medicine and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA. sorokin@post.its.mcw.edu

The docking protein p130(cas) (Crk-associated substrate) forms a stable complex with the adaptor protein CrkII in a tyrosine-phosphorylation-dependent manner. Insulin-induced tyrosine phosphorylation of insulin receptor substrates results in the redistribution of CrkII between p130(cas) and insulin receptor substrate-1. A decrease in the association between CrkII and p130(cas) in response to insulin stimulation was detected in CHO cells stably expressing insulin receptor or insulin receptor substrate-1, and in L6 rat myoblasts. Along with the decrease in the association of CrkII with p130(cas), the amount of tyrosine-phosphorylated insulin receptor substrate-1 co-precipitated with CrkII increased in all cell types studied. The insulin-induced decrease in the CrkII-p130(cas) association was further confirmed by Far Western Blot analysis with the Src homology 2 (SH2) domain of CrkII. Insulin regulates the association of CrkII with p130(cas) by tyrosine dephosphorylation of p130(cas) and co-ordinated tyrosine phosphorylation of insulin receptor substrate-1. Tyrosine-phosphorylated insulin receptor substrate-1 serves as a docking protein for multiple adaptor proteins and competes with p130(cas) for CrkII.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D010750 Phosphoproteins Phosphoprotein
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011494 Protein Kinases A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. Protein Kinase,Kinase, Protein,Kinases, Protein
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D011518 Proto-Oncogene Proteins Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. Cellular Proto-Oncogene Proteins,c-onc Proteins,Proto Oncogene Proteins, Cellular,Proto-Oncogene Products, Cellular,Cellular Proto Oncogene Proteins,Cellular Proto-Oncogene Products,Proto Oncogene Products, Cellular,Proto Oncogene Proteins,Proto-Oncogene Proteins, Cellular,c onc Proteins
D011972 Receptor, Insulin A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE. Insulin Receptor,Insulin Receptor Protein-Tyrosine Kinase,Insulin Receptor alpha Subunit,Insulin Receptor beta Subunit,Insulin Receptor alpha Chain,Insulin Receptor beta Chain,Insulin-Dependent Tyrosine Protein Kinase,Receptors, Insulin,Insulin Receptor Protein Tyrosine Kinase,Insulin Receptors
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D002999 Clone Cells A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed) Clones,Cell, Clone,Cells, Clone,Clone,Clone Cell
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster

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