title: SGK1 sensitivity of platelet migration.
abstract: Recent observations pointed to the ability of platelets to migrate and thus to invade the inflamed vascular wall. Platelet migration could be stimulated by stromal cell-derived factor-1 (SDF-1), an effect dependent on phosphatidylinositide-3-kinase (PI3K) and paralleled by activation and phosphorylation of Wiskott-Aldrich syndrome protein (WASP). Migration is inhibited by vinculin, which is similarly regulated by phosphorylation. PI3K-sensitive kinases include the serum- and glucocorticoid-inducible kinase 1 (SGK1). The present study explored whether SGK1 modifies WASP and vinculin phosphorylation in murine platelets and participates in the regulation of platelet migration. Platelets were isolated from gene-targeted mice lacking SGK1 (sgk1(-/-)) and from their wild type littermates (sgk1(+/+)). Platelet migration stimulated with SDF-1 was significantly less pronounced in sgk1(-/-)platelets than in sgk1(+/+) platelets. Moreover, SDF-1 significantly induced WASP phosphorylation, an effect again reduced in platelets lacking SGK1. Phosphorylation of vinculin was significantly enhanced in sgk1(-/-)platelets and was significantly reduced following treatment of platelets with Ca(2+) chelator BAPTA. Immunohistochemical analysis of in vivo experiments in intestinal vessels after vascular inflammation revealed that transmigration of platelets into inflamed vessel walls was significantly less pronounced in sgk1(-/-)than in sgk1(+/+) mice. In conclusion, SGK1 is a powerful regulator of platelet migration.
authors: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors: Eva-Maria
authors: EM
authors: Schmidt
authors: Bjoern F
authors: BF
authors: Kraemer
authors: Oliver
authors: O
authors: Borst
authors: Patrick
authors: P
authors: Münzer
authors: Tanja
authors: T
authors: Schönberger
authors: Christine
authors: C
authors: Schmidt
authors: Christina
authors: C
authors: Leibrock
authors: Syeda T
authors: ST
authors: Towhid
authors: Peter
authors: P
authors: Seizer
authors: Dietmar
authors: D
authors: Kuhl
authors: Christos
authors: C
authors: Stournaras
authors: Stephan
authors: S
authors: Lindemann
authors: Meinrad
authors: M
authors: Gawaz
authors: Florian
authors: F
authors: Lang
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D054377:Chemokine CXCL12 / Q000502:physiology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply; D007511:Ischemia / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D057705:Transendothelial and Transepithelial Migration; D016596:Vinculin / Q000378:metabolism; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D002614:Chelating Agents; D054377:Chemokine CXCL12; D004533:Egtazic Acid; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D016596:Vinculin; D051316:Wiskott-Aldrich Syndrome Protein; D000099184:Serum-Glucocorticoid Regulated Kinases; C515256:Cxcl12 protein, mouse; C495768:Was protein, mouse; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid