PKD is recruited to sites of actin remodelling at the leading edge and negatively regulates cell migration

Eiseler, Tim; Schmid, Michael A.; Topbas, Fitnat; Pfizenmaier, Klaus; Hausser, Angelika

doi:10.1016/j.febslet.2007.07.079

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Volume 581, Issue 22 , Pages 4279-4287, 4 September 2007

PKD is recruited to sites of actin remodelling at the leading edge and negatively regulates cell migration

Edited by Beat Imhof

Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany

Received 28 March 2007; received in revised form 27 July 2007; accepted 30 July 2007. published online 13 August 2007.

Abstract

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.

Abbreviations: DAG, diacylglycerol, GFP, green fluorescent protein, PKC, protein kinase C, PKD, protein kinase D, PDGF, platelet derived growth factor, TGN, trans Golgi network