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JNK phosphorylates paxillin and regulates cell migration


The c-Jun amino-terminal kinase (JNK) is generally thought to be involved in inflammation, proliferation and apoptosis1,2. Accordingly, its substrates are transcription factors and anti-apoptotic proteins2. However, JNK has also been shown to be required for Drosophila dorsal closure3,4, and MAP kinase/ERK kinase kinase 1, an upstream kinase in the JNK pathway, has been shown to be essential for cell migration5,6. Both results imply that JNK is important in cell migration. Here we show that JNK1 is required for the rapid movement of both fish keratocytes and rat bladder tumour epithelial cells (NBT-II). Moreover, JNK1 phosphorylates serine 178 on paxillin, a focal adhesion adaptor, both in vitro and in intact cells. NBT-II cells expressing the Ser 178 → Ala mutant of paxillin (PaxS178A) formed focal adhesions and exhibited the limited movement associated with such contacts in both single-cell-migration and wound-healing assays. In contrast, cells expressing wild-type paxillin moved rapidly and retained close contacts as the predominant adhesion. Expression of PaxS178A also inhibited the migration of two other cell lines. Thus, phosphorylation of paxillin by JNK seems essential for maintaining the labile adhesions required for rapid cell migration.

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Figure 1: JNK1 is required for cell migration.
Figure 2: Paxillin is phosphorylated at Ser 178 in vitro.
Figure 3: Paxillin is also phosphorylated at Ser 178 in cells.
Figure 4: Expression of PaxS178A inhibits cell migration.a, Expression of PaxS178A changes cell morphology (top panels) and inhibits cell movement (bottom panels).
Figure 5: Expression of PaxS178A promotes focal adhesion formation.


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We thank C. Raska, J. Han and R. M. Pope for their mass spectometric analysis, and K. Burridge, L. Graves and C. Otey for critically reading the manuscript. This study was supported by NIH grants to K.J. and M.D.S., the Cell Migration Consortium to K.J. and the National Institute for Dental and Cranial Research grant to K.J. and M.D.S.

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Correspondence to Ken Jacobson.

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Huang, C., Rajfur, Z., Borchers, C. et al. JNK phosphorylates paxillin and regulates cell migration. Nature 424, 219–223 (2003).

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