The EGF receptor: a nexus for trafficking and signaling

Ligand binding to the EGF receptor initiates both the activation of mitogen ic signal transduction pathways plus trafficking events that relocalize the receptor on the cell surface and within intracellular compartments. The tr afficking compartments include caveolae, clathrin-coated pits, and various endosome populations prior to receptor degradation in lysosomes. Evidence i s presented that distinct signaling pathways are initiated from these diffe rent compartments. These include the Ras/MAP kinase cascade and the PLC-dep endent hydrolysis of PI-4,5 P-2. Multiple tyrosine kinase substrates that f acilitate EGF receptor trafficking between these various compartments, as w ell as the participation of phosphoinositides and Ras-like G proteins in th e trafficking pathway are also described. (C) 2000 John Wiley & Sons, Inc.