Ran binding protein 9 interacts with Raf kinase but does not contribute to downstream ERK1/2 activation in skeletal myoblasts.

Department of Animal Sciences, University of Florida, USA. sjohnson@animal.ufl.edu
Raf kinase is the upstream activator of MEK1/2 leading to phosphorylation and activation of ERK1/2. Sustained activation of Raf represses skeletal muscle-specific reporter gene transcription and formation of multinucleated myofibers. Inhibition of myogenesis by activated Raf involves downstream ERK1/2 as well as undefined mediators. To identify Raf-interacting proteins that may influence repression of muscle formation, a yeast two-hybrid screen was performed using a MEK1-binding defective Raf (RafBXB-T481A) as bait. Twenty cDNAs coding for Raf-interacting proteins were identified including Ran binding protein 9 (RanBP9), a protein previously reported to interact with receptor tyrosine kinases. Forced expression of RanBP9 in myogenic cells did not alter myogenesis. Co-expression of RanBP9 with constitutively active RafBXB, but not RafBXB-T481A, synergistically inhibited MyoD-directed muscle reporter gene transcription. Knockdown of RanBP9 expression did not restore the differentiation program to Raf-expressing myoblasts. Thus, RanBP9 physically associates with Raf but does not substantially contribute to the inhibitory actions of the kinase.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Cell Differentiation, Cytoskeletal Proteins, Enzyme Activation, Gene Silencing, Humans, Mice, Mice, Inbred C3H, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Muscle Development, MyoD Protein, Myoblasts, Skeletal, Nuclear Proteins, Transcription Factor AP-1, raf Kinases, ran GTP-Binding Protein
Biochem. Biophys. Res. Commun. Feb. 10, 2006; 340(2);409-16 [PUBMED:16364241]
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