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 insulin stimulation. In insulin-stimulated 3T3-L1 adipocytes, APS co-precipitated with phosphorylated c-Cbl. In CHO.T-APS cells overexpressing the insulin receptor and APS, APS co-precipitated with c-Cbl but not in CHO.T cells which do not express APS. APS-mediated recruitment of c-Cbl to the insulin receptor led to rapid ubiquitination of the insulin receptor beta-subunit in CHO. T-APS but not in parental CHO.T cells. These results suggest that the function 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 internalisation or degradation.
Ahmed
Z
Z
Molecular Endocrinology Group, Institute of Cell Signalling and School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, NG7 2UH, Nottingham, UK.
Smith
B J
BJ
Pillay
T S
TS
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D008024:Ligands; D010766:Phosphorylation; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases; D018909:src Homology Domains
D008024:Ligands; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D011972:Receptor, Insulin; C067419:CBL protein, human