title: Protein kinase D1-mediated phosphorylations regulate vasodilator-stimulated phosphoprotein (VASP) localization and cell migration.
abstract: Enabled/Vasodilator-stimulated phosphoprotein (Ena/VASP) protein family members link actin dynamics and cellular signaling pathways. VASP localizes to regions of dynamic actin reorganization such as the focal adhesion contacts, the leading edge or filopodia, where it contributes to F-actin filament elongation. Here we identify VASP as a novel substrate for protein kinase D1 (PKD1). We show that PKD1 directly phosphorylates VASP at two serine residues, Ser-157 and Ser-322. These phosphorylations occur in response to RhoA activation and mediate VASP re-localization from focal contacts to the leading edge region. The net result of this PKD1-mediated phosphorylation switch in VASP is increased filopodia formation and length at the leading edge. However, such signaling when persistent induced membrane ruffling and decreased cell motility.
authors.affiliation: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, Florida 32224, USA.
authors.forename: Heike R
authors.initials: HR
authors.lastname: Döppler
authors.forename: Ligia I
authors.initials: LI
authors.lastname: Bastea
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Lewis-Tuffin
authors.forename: Panos Z
authors.initials: PZ
authors.lastname: Anastasiadis
authors.forename: Peter
authors.initials: P
authors.lastname: Storz
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D011554:Pseudopodia / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; C066737:RHOA protein, human; C089212:protein kinase D; D011493:Protein Kinase C; D020742:rhoA GTP-Binding Protein
keywords: Kinase; Phosphorylation; Protein Kinase C (PKC); Protein Kinase D (PKD); Signal Transduction; Signaling; VASP