INSULIN STIMULATES THE TYROSINE DEPHOSPHORYLATION OF DOCKING PROTEIN P130(CAS) (CRK-ASSOCIATED SUBSTRATE), PROMOTING THE SWITCH OF THE ADAPTER PROTEIN CRK FROM P130(CAS) TO NEWLY PHOSPHORYLATED INSULIN-RECEPTOR SUBSTRATE-1

The docking protein p130(cas) (Crk-associated substrate) forms a stabl e 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 p1 30(cas) and insulin receptor substrate-1. A decrease in the associatio n between CrkII and p130(cas) in response to insulin stimulation was d etected in CHO cells stably expressing insulin receptor or insulin rec eptor substrate-1, and in L6 rat myoblasts. Along with the decrease in the association of CrkII with p130(cas), the amount of tyrosine phosp horylated insulin receptor substrate-1 co-precipitated with CrkII incr eased in all cell types studied. The insulin-induced decrease in the C rkII-p130(cas) association was further confirmed by Far Western Blot a nalysis with the Src homology 2 (SH2) domain of CrkII. Insulin regulat es the association of CrkII with p130(cas) by tyrosine dephosphorylati on of p130(cas) and coordinated tyrosine phosphorylation of insulin re ceptor substrate-1. Tyrosine-phosphorylated insulin receptor substrate -1 serves as a docking protein for multiple adaptor proteins and compe tes with p130(cas) for CrkII.