SGK1 Sensitivity of Platelet Migration

Cellular Physiology and Biochemistry

关键词: SDF-1;    WASP;    Vinculin;    SGK1;    Platelets;    Migration;   

DOI  :  10.1159/000339062

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

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 Ca²⁺ 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.

【 授权许可】

CC BY-NC-ND