JNK pathway-associated phosphatase dephosphorylates focal adhesion kinase and suppresses cell migration.
JNK pathway-associated phosphatase (JKAP, also named DUSP22) is expressed in various tissues, indicating that JKAP may have an important biological function. We showed that JKAP localized in the actin filament-enriched region. Expression of JKAP reduced cell migration, whereas a JKAP mutant lacking catalytic activity promoted cell motility. JKAP efficiently removed tyrosine phosphorylation of several proteins. We have identified focal adhesion kinase (FAK) as a substrate of JKAP. Overexpression of JKAP, but not JKAP mutant lacking catalytic activity, decreased FAK phosphorylation at tyrosines 397, 576, and 577 in H1299 cells. Consistent with these results, decreasing JKAP expression by RNA interference promoted cell migration and Src-induced FAK phosphorylation. Taken together, this study identified a new role for JKAP in the modulation of FAK phosphorylation and cell motility.
Li
Ju-Pi
JP
Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli County 35053, Taiwan.
Fu
Yu-Ning
YN
Chen
Yi-Rong
YR
Tan
Tse-Hua
TH
D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D054637:Dual-Specificity Phosphatases / Q000235:genetics / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D034622:RNA Interference; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism
D014443:Tyrosine; D051417:Focal Adhesion Kinase 1; D015688:Oncogene Protein pp60(v-src); C496050:PTK2 protein, human; D054639:Mitogen-Activated Protein Kinase Phosphatases; C442824:DUSP22 protein, human; D054637:Dual-Specificity Phosphatases