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

FEBS Lett. 2002 Dec 18;532(3):445-9. doi: 10.1016/s0014-5793(02)03736-5.

Abstract

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 / metabolism
  • COS Cells
  • Catalysis
  • Chromosome Mapping
  • DNA, Complementary / metabolism
  • Dimerization
  • Genetic Vectors
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • PC12 Cells
  • Peptides
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Precipitin Tests
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / physiology*
  • Rats
  • Signal Transduction
  • Transfection
  • Tumor Cells, Cultured
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • DNA, Complementary
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Peptides
  • Phosphoproteins
  • collapsin response mediator protein-1
  • collapsin response mediator protein-2
  • Protein-Serine-Threonine Kinases
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein