p80 ROKalpha binding protein is a novel splice variant of CRMP-1 which associates with CRMP-2 and modulates RhoA-induced neuronal morphology.
Using antibody against the Rho binding domain of ROKalpha, two neuronal phosphoproteins of 62 and 80 kDa were co-immunoprecipitated from brain extracts. Peptide analysis revealed their identity as collapsin response mediator proteins (CRMPs); p62 was CRMP-2 whereas p80 was a novel splice form of CRMP-1 with an extended N-terminus. p80 ... CRMP-1 was able to complex with CRMP-2, suggesting that p80 CRMP-1 and CRMP-2 form oligomers. CRMP-2 was the major substrate of ROK. p80 CRMP-1 interacted with the kinase domain of ROKalpha, resulting in inhibition of the catalytic activity towards other substrates. Over-expression of p80 CRMP-1 and CRMP-2 together counteracted the effects of RhoA on neurite retraction, an effect enhanced by mutation of the ROK phosphorylation site in CRMP-2. p80 CRMP-1 and CRMP-2 may be modulators of RhoA-dependent signaling, through interaction with and regulation of ROKalpha.
Mesh Terms:
Alternative Splicing, Amino Acid Sequence, Animals, Blotting, Western, Brain, COS Cells, Catalysis, Chromosome Mapping, DNA, Complementary, Dimerization, Genetic Vectors, Humans, Intercellular Signaling Peptides and Proteins, Intracellular Signaling Peptides and Proteins, Mice, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, PC12 Cells, Peptides, Phosphoproteins, Phosphorylation, Precipitin Tests, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Rats, Signal Transduction, Transfection, Tumor Cells, Cultured, rho-Associated Kinases, rhoA GTP-Binding Protein
Alternative Splicing, Amino Acid Sequence, Animals, Blotting, Western, Brain, COS Cells, Catalysis, Chromosome Mapping, DNA, Complementary, Dimerization, Genetic Vectors, Humans, Intercellular Signaling Peptides and Proteins, Intracellular Signaling Peptides and Proteins, Mice, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, PC12 Cells, Peptides, Phosphoproteins, Phosphorylation, Precipitin Tests, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Rats, Signal Transduction, Transfection, Tumor Cells, Cultured, rho-Associated Kinases, rhoA GTP-Binding Protein
FEBS Lett.
Date: Dec. 18, 2002
PubMed ID: 12482610
View in: Pubmed Google Scholar
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