PKD is recruited to sites of actin remodelling at the leading edge and negatively regulates cell migration.
Protein kinase D (PKD) has been implicated in the regulation of cell shape, adhesion, and migration. At the leading edge of migrating cells active PKD co-localizes with F-actin, Arp3 and cortactin. Platelet derived growth factor (PDGF) activates PKD and recruits the kinase to the leading edge, suggesting a role for PKD in actin remodelling. In support of this, PKD directly interacts with F-actin and phosphorylates cortactin in vitro. Interference with PKD function by overexpression of a dominant negative PKD or by PKD-specific siRNA enhanced cell migration, whereas cells overexpressing PKD wild type displayed reduced migratory potential. Taken together, these data reveal a negative regulatory function of PKD in cell migration.
Eiseler
Tim
T
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
Schmid
Michael A
MA
Topbas
Fitnat
F
Pfizenmaier
Klaus
K
Hausser
Angelika
A
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement; D051356:Cortactin / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D021381:Protein Transport; D011554:Pseudopodia / Q000201:enzymology*
D000199:Actins; D051356:Cortactin; C089212:protein kinase D; D011493:Protein Kinase C