The EGF receptor: a nexus for trafficking and signaling.
Ligand binding to the EGF receptor initiates both the activation of mitogenic signal transduction pathways plus trafficking events that relocalize the receptor on the cell surface and within intracellular compartments. The trafficking compartments include caveolae, clathrin-coated pits, and various endosome populations prior to receptor degradation in lysosomes. Evidence is presented that distinct signaling pathways are initiated from these different compartments. These include the Ras/MAP kinase cascade and the PLC-dependent hydrolysis of PI-4,5 P(2). Multiple tyrosine kinase substrates that facilitate EGF receptor trafficking between these various compartments, as well as the participation of phosphoinositides and Ras-like G proteins in the trafficking pathway are also described.
Department of Biochemistry, Vanderbilt University School of Medicine Nashville, TN 37232-0146, USA. Graham.Carpenter@mcmail.vanderbilt.edu
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D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D010716:Phosphatidylinositols / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
D002966:Clathrin; D066246:ErbB Receptors; D019204:GTP-Binding Proteins; D010716:Phosphatidylinositols; D018719:Erb-b2 Receptor Tyrosine Kinases; D019061:src-Family Kinases