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Author Song, Mia ♦ He, Qianjing ♦ Berk, Benjamin-Andreas ♦ Hartwig, John H. ♦ Stossel, Thomas P. ♦ Nakamura, Fumihiko
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ACTIN ♦ AMINO ACIDS ♦ BLADDER ♦ FILAMENTS ♦ HYBRID SYSTEMS ♦ HYBRIDIZATION ♦ LIGANDS ♦ METASTASES ♦ MUTANTS ♦ MUTATIONS ♦ NEOPLASMS ♦ PHOSPHORYLATION ♦ YEASTS
Abstract Filamin A (FLNA) is an actin filament crosslinking protein with multiple intracellular binding partners. Mechanical force exposes cryptic FLNA binding sites for some of these ligands. To identify new force-dependent binding interactions, we used a fusion construct composed of two FLNA domains, one of which was previously identified as containing a force-dependent binding site as a bait in a yeast two-hybrid system and identified the Rho dissociation inhibitor 2 (RhoGDI2) as a potential interacting partner. A RhoGDI2 truncate with 81 N-terminal amino acid residues and a phosphomimetic mutant, RhoGDI(Tyr153Glu) interacted with the FLNA construct. However, neither wild-type or full-length RhoGDI2 phosphorylated at Y153 interacted with FLNA. Our interpretation of these contradictions is that truncation and/or mutation of RhoGDI2 perturbs its conformation to expose a site that adventitiously binds FLNA and is not a bona–fide interaction. Therefore, previous studies reporting that a RhoGDI(Y153E) mutant suppresses the metastasis of human bladder cancer cells must be reinvestigated in light of artificial interaction of this point mutant with FLNA. - Highlights: • RhoGDI2 is identified as a potential filamin A (FLNA)-binding partner. • Phosphomimetic mutant, RhoGDI2(Tyr153Glu) interacts with FLNA. • RhoGDI2 phosphorylated (Tyr153) by src kinase does not interact with FLNA. • Mutation of Tyr-153 to Glu of RhoGDI2 does not mimic phosphorylation. • RhoGDI2(Tyr153Glu) provokes an adventitious interaction with FLNA.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-01-15
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 469
Issue Number 3


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