Figure Legend: Tom1L1 contains a novel clathrin-binding motif important for endocytosis of EGFR. A working model for Tom1L1 to act as a regulated adaptor mediating EGF-stimulated endocytosis of EGFR. On EGF stimulation, EGFR dimerizes, leading to the activation of its cytoplasmic kinase domain and Tyr-phosphorylation at multiple sites, which then serve as docking sites for various signalling proteins such as Shc/Grb2 and Src kinases; activated Src family kinases phosphorylate Y460 of Tom1L1, causing a transient interaction of pTom1L1 with the activated EGFR through Grb2/Shc. By interacting with clathrin, pTom1L1 can bring endocytic machinery to mediate the segregation of activated EGFR into clathrin-coated structures for endocytosis. Other proteins such as dynamin and c-Cbl may be independently recruited to complete the endocytosis. After endocytosis, pTom1L1 becomes dephosphorylated and the dephosphorylated Tom1L1 is retained on the early endosome probably through its interaction with Hrs and TSG101 (Puertollano, 2005), in which it may potentially facilitate the sorting of EGFR into the MVB .
Published in The EMBO Journal online publication
( 1 October 2009/emboj 2009282)
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