p80 ROKα binding protein is a novel splice variant of CRMP‐1 which associates with CRMP‐2 and modulates RhoA‐induced neuronal morphology

FEBS Letters

Hall, Christine¹  Tan, Ivan²  Ng, Chong Han²  Leung, Thomas²  Ng, Yvonne²  Lim, Louis²  Cheong, Albert² 

[1] Department of Molecular Pathogenesis, Institute of Neurology, UCL, 1 Wakefield Street, London WC1N 1PJ, UK;Glaxo-IMCB Group, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609

关键词: ROKα;    CRMP family;    RhoA;    Neuronal morphology;    CRMP;    collapsin response mediator protein;    ROK;    RhoA binding kinase;    MLC2;    myosin light chain 2;    Sema3A;    semaphorin 3A;    LPA;    lipophosphatidic acid;    NGF;    nerve growth factor;   

DOI  :  10.1016/S0014-5793(02)03736-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Using antibody against the Rho binding domain of ROKα, 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 ROKα, 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 ROKα.

【 授权许可】

Unknown