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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line
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Cytoskeletal Proteins / metabolism
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DNA-Binding Proteins / metabolism*
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Endosomes / drug effects
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Endosomes / metabolism
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Hepatocyte Growth Factor / pharmacology*
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Humans
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Hyaluronan Receptors / chemistry
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Hyaluronan Receptors / metabolism*
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Protein Binding
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Protein Interaction Domains and Motifs
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Protein Transport / drug effects
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Proto-Oncogene Proteins c-met / metabolism*
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Proto-Oncogene Proteins p21(ras) / metabolism
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Signal Transduction
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Transcription Factors / metabolism*
Substances
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CD44v6 antigen
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Cytoskeletal Proteins
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DNA-Binding Proteins
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ETV5 protein, human
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Hyaluronan Receptors
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Transcription Factors
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ezrin
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Hepatocyte Growth Factor
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Proto-Oncogene Proteins c-met
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Proto-Oncogene Proteins p21(ras)
Grants and funding
This work was supported by grants of the Deutsche Forschungsgemeinschaft (SPP1190 and OR 124/7-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.