Characterization of Ligand-Induced Endocytosis of EGF-Receptors

摘要

Under the auspices of this training Fellowship (May 9, 1994-November 9, 1997), Ihave undertaken studies on the molecular mechanisms that govern ligand-induced endocytosis of epidermal growth factor receptors (EGFR) and the role of regulated endocytosis of EGFR in controlling EGFR signaling. To this end, I developed a novel cell-free assay which reconstitutes the ligand-induced and EGFR tyrosine kinase-dependent recruitment of EGFR into cathrine coated pits. I also showed that activation of small Rho-family GTPases, which occurs in response to growth factors, can negatively regulate receptor-mediated endocytosis. In following up this discovery, I have provided new and direct evidence for the involvement of the actin cytoskeleton in early events in receptor-mediated endocytosis. Finally, I have begun to explore the role of an EGFR tyrosine kinase substrate, Eps15, in receptor-mediated endocytosis. Eps15 is the prototype member of a growing family of EH (Eps15-homology) domain-containing proteins required for intracellular membrane trafficking.