title: Met receptor: a moving target.
abstract: The activated hepatocyte growth factor (HGF) receptor (Met) undergoes rapid endocytosis and ubiquitin-dependent sorting to the lysosomal degradative pathway. New data suggest that this mode of down-regulation can be circumvented by mutant receptors bearing kinase-activating mutations that instead recycle to the plasma membrane. These mutant receptors can elicit enhanced signaling from endosomes, which is critical for cell motility and tumorigenesis. A proportion of HGF-activated wild-type receptors will also take the endosomal recycling route. This requires the recruitment of the adaptor protein GGA3, mediated through the interaction of GGA3 with the activated form of the small guanosine triphosphatase Arf6 and indirect binding to phosphorylated Met receptor through the adaptor protein Crk. This ability of receptors and effectors to be spatially controlled by the endosomal recycling pathway may play a prominent role in cellular functions such as motility.
authors.affiliation: Physiological Laboratory, Institute of Translational Medicine, University of Liverpool, Crown Street, L69 3BX, Liverpool, UK. clague@liv.ac.uk
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Clague
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D059748:Proteolysis; D050737:Proto-Oncogene Proteins c-crk / Q000235:genetics / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism
chemical_list: D000089982:ADP-Ribosylation Factor 6; D033942:Adaptor Proteins, Vesicular Transport; C485285:CRK protein, human; C407306:GGA adaptor proteins; D050737:Proto-Oncogene Proteins c-crk; D014452:Ubiquitins; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human