Focal adhesion kinase regulates laminin-induced oligodendroglial process outgrowth.
In the central nervous system (CNS), myelination of axons occurs when oligodendrocyte progenitor cells undergo terminal differentiation, and initiate process formation and axonal ensheathment. Although Fyn, a member of the Src-family kinases (SFKs), plays an important role in this differentiation process, the substrates of Fyn in oligodendrocytes are largely unknown. Using mass spectrometric analysis, we identified focal adhesion kinase (FAK) as a tyrosine-phosphorylated protein in the rat-derived CG4 oligodendrocyte cell line. Tyrosine phosphorylation of FAK was enhanced during differentiation of CG4 cells in a Fyn-dependent manner. In addition, phosphorylation of FAK was stimulated by laminin, one of the ligands for integrin. Knockdown of FAK expression in CG4 cells suppressed process outgrowth on laminin. Rac1 and Cdc42 activities, which are required for oligodendrocyte process formation, were down-regulated in FAK-knockdown cells. Expression of wild-type (WT) FAK in FAK-knockdown CG4 cells restored outgrowth of processes, but the Y397F mutant lacking the autophosphorylation site did not. These results suggest that FAK/Fyn-mediated activation of Rac1 and Cdc42 is critical for laminin-induced outgrowth of oligodendrocyte processes.
Hoshina
Naosuke
N
Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Tezuka
Tohru
T
Yokoyama
Kazumasa
K
Kozuka-Hata
Hiroko
H
Oyama
Masaaki
M
Yamamoto
Tadashi
T
D000818:Animals; D045744:Cell Line, Tumor; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D007797:Laminin; D014443:Tyrosine; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D019061:src-Family Kinases; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein