Proceedings of the National Academy of Sciences - PNAS, 2007-06, Vol.104 (25), p.10465-10469
2007
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- Autor(en) / Beteiligte
- Titel
- IQGAP1 modulates activation of B-Raf
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2007-06, Vol.104 (25), p.10465-10469
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2007
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- IQGAP1 modulates several cellular functions, including cell-cell adhesion, transcription, cytoskeletal architecture, and selected signaling pathways. We previously documented that IQGAP1 binds ERK and MAPK kinase (MEK) and regulates EGF-stimulated MEK and ERK activity. Here we characterize the interaction between IQGAP1 and B-Raf, the molecule immediately upstream of MEK in the Ras/MAPK signaling cascade. B-Raf binds directly to IQGAP1 in vitro and coimmunoprecipitates with IQGAP1 from cell lysates. Importantly, IQGAP1 modulates B-Raf function. EGF is unable to stimulate B-Raf activity in IQGAP1-null cells and in cells transfected with an IQGAP1 mutant construct that is unable to bind B-Raf. Interestingly, binding to IQGAP1 significantly enhances B-Raf activity in vitro. Our data identify a previously unrecognized interaction between IQGAP1 and B-Raf and suggest that IQGAP1 is a scaffold necessary for activation of B-Raf by EGF.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.0611308104Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1965536
- Format
- –
- Schlagworte
- Amino acids, Animals, Antibodies, Biochemistry, Biological Sciences, Cell Line, Transformed, Cells, Cultured, Cellular biology, Culture Media, Serum-Free, Embryo, Mammalian, Enzyme Activation, Epidermal Growth Factor - pharmacology, Fibroblasts - cytology, Fibroblasts - metabolism, Gene expression regulation, Glutathione Transferase - metabolism, Humans, Kinases, Mice, Mice, Knockout, Modulated signal processing, Monoclonal antibodies, Mutation, Phosphatases, Plasmids - metabolism, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Proteins, Proto-Oncogene Proteins B-raf - analysis, Proto-Oncogene Proteins B-raf - metabolism, ras GTPase-Activating Proteins - chemistry, ras GTPase-Activating Proteins - genetics, ras GTPase-Activating Proteins - metabolism, Receptors, Recombinant Fusion Proteins - metabolism, Scaffolds, Small interfering RNA, Time Factors, Transfection, Western blotting