JNK Acts at Focal Adhesions

The c-Jun amino-terminal kinase (JNK) has been thought to function solely in the nucleus where its targets have been identified. But activated JNK has also been detected in cellular focal adhesions, complexes at the cell surface that mediate cell adhesion, and JNK activation has also been associated with increased cell migration in numerous cell types. Huang et al. now confirm a role for JNK outside of the nucleus in which JNK appears to phosphorylate a focal adhesion component called paxillin, an adaptor protein that organizes focal adhesions. JNK phosphorylation is activated when cells are exposed to growth factors and extracellular matrix proteins that stimulate motility. Treatment of different cell types, including mammalian fibroblasts and fast-moving fish keratocytes, with a pharmacological inhibitor of JNK arrested cell motility. Overexpression of a dominant-negative form of JNK induced focal adhesion formation and also inhibited cell movement. Activated JNK phosphorylated recombinant paxillin at Ser 178 , and endogenous paxillin was similarly phosphorylated when cells were treated with growth factor. A mutant form of paxillin lacking this phosphorylation site localized to focal adhesion structures, whereas wild-type paxillin was more diffusely distributed along the cell edge. The authors propose that phosphorylation of paxillin by JNK may promote focal adhesion turnover, which allows cell to move. This JNK-paxillin connection may be a common downstream target of numerous signaling pathways implicated in regulating adhesion dynamics and cell movement. C. Huang, Z. Rajfur, C. Borchers, M.D. Schaller, K. Jacobson, JNK phosphorylates paxillin and regulates cell migration. Nature 424 , 219-223 (2003). [Online Journal]