title: Internalization of Met requires the co-receptor CD44v6 and its link to ERM proteins.
abstract: Receptor Tyrosine Kinases (RTKs) are involved in many cellular processes and play a major role in the control of cell fate. For these reasons, RTK activation is maintained under tight control. Met is an essential RTK that induces proliferation, differentiation, migration, survival and branching morphogenesis. Deregulation of Met by overexpression, amplification or lack of effective degradation leads to cancer and metastasis. We have shown that Met relies on CD44v6 for its activation and for signaling in several cancer cell lines and also in primary cells. In this paper, we show that internalization of Met is dependent on CD44v6 and the binding of Ezrin to the CD44v6 cytoplasmic domain. Both CD44v6 and Met are co-internalized upon Hepatocyte Growth Factor induction suggesting that Met-induced signaling from the endosomes relies on its collaboration with CD44v6 and the link to the cytoskeleton provided by ERM proteins.
authors.affiliation: Karlsruhe Institute of Toxicology, Institute for Toxicology and Genetics, Karlsruhe, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Hasenauer
authors.forename: Dieter
authors.initials: D
authors.lastname: Malinger
authors.forename: David
authors.initials: D
authors.lastname: Koschut
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Pace
authors.forename: Alexandra
authors.initials: A
authors.lastname: Matzke
authors.forename: Anja
authors.initials: A
authors.lastname: von Au
authors.forename: Véronique
authors.initials: V
authors.lastname: Orian-Rousseau
mesh_terms: D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport / Q000187:drug effects; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D017228:Hepatocyte Growth Factor; D018960:Hyaluronan Receptors; D019859:Proto-Oncogene Proteins c-met; D016283:Proto-Oncogene Proteins p21(ras); D014157:Transcription Factors; D000099149:Ezrin; C112697:CD44v6 antigen; C086680:ETV5 protein, human