The APS adapter protein couples the insulin receptor to the phosphorylation of c-Cbl and facilitates ligand-stimulated ubiquitination of the insulin receptor

The APS adapter protein is rapidly tyrosine-phosphorylated following insuli n stimulation. In insulin-stimulated 3T3-L1 adipocytes, APS co-precipitated with phosphorylated c-Cbl. In CHO.T-APS cells overexpressing the insulin r eceptor and APS, APS co-precipitated with c-Cbl but not in CHO.T cells whic h do not express APS. APS-mediated recruitment of c-Cbl to the insulin rece ptor led to rapid ubiquitination of the insulin receptor beta-subunit in CH O.T-APS but not in parental CHO.T cells. These results suggest that the fun ction of APS is to facilitate coupling of the insulin receptor to c-Cbl in order to catalyse the ubiquitination of the receptor and initiation of inte rnalisation or degradation. (C) 2000 Federation of European Biochemical Soc ieties. Published by Elsevier Science B.V. All rights reserved.