JNK phosphorylates paxillin and regulates cell migration.
The c-Jun amino-terminal kinase (JNK) is generally thought to be involved in inflammation, proliferation and apoptosis. Accordingly, its substrates are transcription factors and anti-apoptotic proteins. However, JNK has also been shown to be required for Drosophila dorsal closure, and MAP kinase/ERK kinase kinase 1, an upstream kinase in the JNK pathway, has been shown to be essential for cell migration. 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 (Pax(S178A)) 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 Pax(S178A) 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.
Huang
Cai
C
Department of Cell and Developmental Biology, Comprehensive Center for Inflammatory Disorders, University of North Carolina, Chapel Hill, North Carolina 27599-7090, USA.
Rajfur
Zenon
Z
Borchers
Christoph
C
Schaller
Michael D
MD
Jacobson
Ken
K
D000595:Amino Acid Sequence; D000818:Animals; D000873:Anthracenes; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors; D005399:Fishes; D022001:Focal Adhesions / Q000502:physiology; D049452:Green Fluorescent Proteins; D006801:Humans; D066298:In Vitro Techniques; D008164:Luminescent Proteins; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D051419:Paxillin; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D012694:Serine / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection; D014407:Tumor Cells, Cultured
D000873:Anthracenes; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D008164:Luminescent Proteins; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; C496063:Pxn protein, rat; D049452:Green Fluorescent Proteins; C432165:pyrazolanthrone; D012694:Serine; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases