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Involvement of Fes/Fps tyrosine kinase in semaphorin3A signaling
Author(s) -
Mitsui Norihiro,
Inatome Ryoko,
Takahashi Shusuke,
Goshima Yoshio,
Yamamura Hirohei,
Yanagi Shigeru
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf328
Subject(s) - biology , tyrosine kinase , signal transduction , tyrosine , microbiology and biotechnology , biochemistry
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.