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Protein kinase A‐dependent increase in WAVE2 expression induced by the focal adhesion protein vinexin
Author(s) -
Mitsushima Masaru,
Sezaki Takuhito,
Akahane Rie,
Ueda Kazumitsu,
Suetsugu Shiro,
Takenawa Tadaomi,
Kioka Noriyuki
Publication year - 2006
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2006.00932.x
Subject(s) - microbiology and biotechnology , biology , signal transducing adaptor protein , focal adhesion , protein kinase a , phosphatase , kinase , immunoprecipitation , guanine nucleotide exchange factor , phosphorylation , signal transduction , biochemistry , gene
The focal adhesion protein vinexin is a member of a family of adaptor proteins that are thought to participate in the regulation of cell adhesion, cytoskeletal reorganization, and growth factor signaling. Here, we show that vinexin β increases the amount of and reduces the mobility on SDS‐PAGE of Wiskott‐Aldrich syndrome protein family verprolin‐homologous protein (WAVE) 2 protein, which is a key factor modulating actin polymerization in migrating cells. This mobility retardation disappeared after in vitro phosphatase treatment. Co‐immunoprecipitation assays revealed the interaction of vinexin β with WAVE2 as well as WAVE1 and N‐WASP. Vinexin β interacts with the proline‐rich region of WAVE2 through the first and second SH3 domains of vinexin β. Mutations disrupting the interaction impaired the ability of vinexin β to increase the amount of WAVE2 protein. Treatments with proteasome inhibitors increased the amount of WAVE2, but did not have an additive effect with vinexin β. Inhibition of protein kinase A (PKA) activity suppressed the vinexin‐induced increase in WAVE2 protein, while activation of PKA increased WAVE2 expression without vinexin β. These results suggest that vinexin β regulates the proteasome‐dependent degradation of WAVE2 in a PKA‐dependent manner.