FAK/src-family dependent activation of the Ste20-like kinase SLK is required for microtubule-dependent focal adhesion turnover and cell migration.
Cell migration involves a multitude of signals that converge on cytoskeletal reorganization, essential for development, immune responses and tissue repair. Using knockdown and dominant negative approaches, we show that the microtubule-associated Ste20-like kinase SLK is required for focal adhesion turnover and cell migration downstream of the FAK/c-src complex. Our results show that SLK co-localizes with paxillin, Rac1 and the microtubules at the leading edge of migrating cells and is activated by scratch wounding. SLK activation is dependent on FAK/c-src/MAPK signaling, whereas SLK recruitment to the leading edge is src-dependent but FAK independent. Our results show that SLK represents a novel focal adhesion disassembly signal.
Wagner
Simona
S
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Storbeck
Chris J
CJ
Roovers
Kristin
K
Chaar
Ziad Y
ZY
Kolodziej
Piotr
P
McKay
Marlene
M
Sabourin
Luc A
LA
D016475:3T3 Cells; D000818:Animals; D002465:Cell Movement; D005347:Fibroblasts / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000502:physiology; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D000099317:Hippo Kinases
D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); D034741:RNA, Small Interfering; C402650:SLK protein, mouse; D000099317:Hippo Kinases