Dab2 links CIN85 with clathrin-mediated receptor internalization.
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.
Ludwig Institute for Cancer Research, Husargatan 3, Uppsala 75124, Sweden.
Katarzyna
K
Kowanetz
Janos
J
Terzic
Ivan
I
Dikic
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism* / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D002460:Cell Line; D022163:Clathrin-Coated Vesicles; D017124:Conserved Sequence; D004705:Endocytosis; D016147:Genes, Tumor Suppressor; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D051379:Mice; D011485:Protein Binding; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D014162:Transfection; D025521:Tumor Suppressor Proteins; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; C102885:DAB2 protein, human; D006133:Growth Substances; D025521:Tumor Suppressor Proteins; D020794:Receptor Protein-Tyrosine Kinases