Involvement of Fes/Fps tyrosine kinase in semaphorin3A signaling.
Collapsin response mediator proteins (CRMPs)/TOAD64/Ulips/DRPs and CRAM have emerged as strong candidates for a role in semaphorin signaling. In this study we identified Fes/Fps (Fes) tyrosine kinase in the CRMP-CRAM complex and investigated whether Fes was involved in semaphorin3A (Sema3A) signaling. In COS-7 cells, the interaction between Fes and plexinA1 (PlexA1) and the tyrosine phosphorylation of PlexA1 by Fes were observed; however, these events were significantly attenuated by co-expression of neuropilin-1 (NP-1). Even with NP-1 co-expression, Sema3A was able to enhance the association of Fes with PlexA1 and Fes-mediated tyrosine phosphorylation of PlexA1, CRAM and CRMP2. Co-expression of Fes with PlexA1 exhibited COS-7 cell contraction activity, indicating that Fes can convert inactive PlexA1 to its active form, whereas combination of Fes/NP-1/PlexA1 or Fes kinase-negative mutants/PlexA1 did not alter cell morphology. Finally, Sema3A-induced growth cone collapse of dorsal root ganglion neurons was suppressed by expression of Fes kinase-negative mutants. Taken together, our findings suggest that Fes links Sema3A signals to CRMP-CRAM, and that NP-1 negatively regulates PlexA1 activation by Fes in resting condition.
Mitsui
Norihiro
N
Division of Proteomics, Department of Genome Sciences, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, 650-0017, Japan.
Inatome
Ryoko
R
Takahashi
Shusuke
S
Goshima
Yoshio
Y
Yamamura
Hirohei
H
Yanagi
Shigeru
S
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001921:Brain / Q000201:enzymology*; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism; D002522:Chlorocebus aethiops; D005727:Ganglia, Spinal / Q000166:cytology; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D009475:Neurons, Afferent / Q000378:metabolism / Q000648:ultrastructure; D039942:Neuropilin-1; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D051578:Proto-Oncogene Proteins c-fes; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000502:physiology; D040121:Semaphorin-3A; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C413755:Dpysl5 protein, rat; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; C492116:PLXNA1 protein, human; C492114:Plxna1 protein, mouse; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D040121:Semaphorin-3A; C095114:collapsin response mediator protein-2; C052602:proto-oncogene protein c-fes-fps; D039942:Neuropilin-1; D011505:Protein-Tyrosine Kinases; C496645:FES protein, human; C496646:Fes protein, mouse; D051578:Proto-Oncogene Proteins c-fes