Dab2 links CIN85 with clathrin‐mediated receptor internalization

FEBS Letters

Dikic, Ivan²  Kowanetz, Katarzyna²  Terzic, Janos¹ 

[1] Department of Immunology, University of Split Medical School, Soltanska 2, 21000 Split, Croatia;Ludwig Institute for Cancer Research, Husargatan 3, Uppsala 75124, Sweden

关键词: AP-2;    CIN85;    Clathrin;    Dab2;    Epidermal growth factor (receptor);    AP-2;    adaptor protein 2;    CIN85;    Cbl interacting protein of 85kDa;    Dab2;    disabled-2;    EGF(R);    epidermal growth factor (receptor);    GST;    glutathione S-transferase;    RTK;    receptor tyrosine kinase;    SH3 domain;    Src homology 3 domain;   

DOI  :  10.1016/S0014-5793(03)01111-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

CIN85 is a multidomain scaffold protein involved in downregulation of receptor tyrosine kinases. Here we show that disabled-2 (Dab2), an endocytic adaptor molecule implicated in clathrin-coat assembly, associates with CIN85 in mammalian cells. All three SH3 domains of CIN85 were able to bind to the PKPAPR peptide in the carboxyl-terminal part of Dab2, possibly enabling CIN85 to simultaneously interact with multiple Dab2 molecules. CIN85 association with Dab2 is essential for its recruitment to clathrin coat and appears to be modulated by growth factor stimulation. Dab2 and clathrin dissociated from CIN85 following growth factor treatment, enabling other molecules, such as Cbl, to bind to CIN85. Taken together, our data indicate a dynamic interplay between CIN85 and its effectors during endocytosis of receptor tyrosine kinases.

【 授权许可】

Unknown