Open AccessY ersinia protein kinase A phosphorylates vasodilator‐stimulated phosphoprotein to modify the host cytoskeleton
Author(s) -
Ke Yuehua,
Tan Yafang,
Wei Na,
Yang Fen,
Yang Huiying,
Cao Shiyang,
Wang Xiaohui,
Wang Jian,
Han Yanping,
Bi Yujing,
Cui Yujun,
Yan Yanfeng,
Song Yajun,
Yang Xiaoming,
Du Zongmin,
Yang Ruifu
Publication year - 2015
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12378
Subject(s) - microbiology and biotechnology , rhoa , biology , actin cytoskeleton , wiskott–aldrich syndrome protein , cytoskeleton , effector , pak1 , phosphorylation , kinase , membrane ruffling , protein kinase domain , signal transduction , biochemistry , cell , gene , mutant
Summary Pathogenic Y ersinia species evolved a type III secretion system that injects a set of effectors into the host cell cytosol to promote infection. One of these effectors, Y ersinia protein kinase A ( YpkA ), is a multidomain effector that harbours a S er/ T hr kinase domain and a guanine dissociation inhibitor ( GDI ) domain. The intercellular targets of the kinase and GDI domains of YpkA were identified to be Gαq and the small GTP ases RhoA and R ac1, respectively, which synergistically induce cytotoxic effects on infected cells. In this study, we demonstrate that vasodilator‐stimulated phosphoprotein ( VASP ), which is critical for regulation of actin assembly, cell adhesion and motility, is a direct substrate of YpkA kinase activity. Ectopic co‐expression of YpkA and VASP in HEK293T cells leads to the phosphorylation of VASP at S157, and YpkA kinase activity is essential for VASP phosphorylation at this site. Moreover, YpkA directly phosphorylates VASP in in vitro kinase assay. YpkA ‐mediated VASP phosphorylation significantly inhibits actin polymerization and promotes the disruption of actin cytoskeleton, which inhibits the phagocytosis. Taken together, our study found a novel molecular mechanism used by YpkA to disrupt cytoskeleton dynamics, thereby promoting the anti‐phagocytosis ability of pathogenic Y ersiniae .