p250GAP, a neural RhoGAP protein, is associated with and phosphorylated by Fyn.
Fyn is a member of the Src-family protein tyrosine kinases and plays important roles in both neurons and oligodendrocytes. Here we report association of Fyn with p250GAP, a RhoGAP protein that is expressed predominantly in brain. p250GAP interacts with Fyn both in vitro and in vivo. p250GAP is tyrosine phosphorylated by Fyn when co-expressed in HEK293T cells. This phosphorylation appears to enhance the interaction between p250GAP and Fyn. Furthermore, the level of tyrosine phosphorylation of p250GAP increases upon differentiation of the oligodendrocyte cell line CG4. Given that Fyn activity is up-regulated during oligodendrocyte maturation, the results argue that p250GAP is phosphorylated by Fyn in oligodendrocytes. Tyrosine phosphorylation of p250GAP by Fyn would regulate its RhoGAP activity, subcellular localization, or interactions with other proteins, leading to morphological and phenotypic changes of oligodendrocytes.
Taniguchi
Sachiko
S
Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan.
Liu
Hui
H
Nakazawa
Takanobu
T
Yokoyama
Kazumasa
K
Tezuka
Tohru
T
Yamamoto
Tadashi
T
D002454:Cell Differentiation; D002460:Cell Line; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C470196:ARHGAP32 protein, human; D020690:GTPase-Activating Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; D020741:rho GTP-Binding Proteins