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

FEBS Letters

Ahmed, Z¹  Pillay, T.S¹  Smith, B.J¹ 

[1] Molecular Endocrinology Group, Institute of Cell Signalling and School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK

关键词: Insulin receptor;    Tyrosine kinase;    c-Cbl;    Adapter protein containing a PH and SH2 domain;    Adapter protein;    Ubiquitination;    APS;    adapter protein containing a PH and SH2 domain;    CHO;    Chinese hamster ovary;    IRS;    insulin receptor substrate;    SH2;    Src homology 2;    PDGF;    platelet-derived growth factor;   

DOI  :  10.1016/S0014-5793(00)01621-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 β-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.

【 授权许可】

Unknown