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Biochem Biophys Res Commun. 2016 Jan 15;469(3):659-64. doi: 10.1016/j.bbrc.2015.12.044. Epub 2015 Dec 17.

An adventitious interaction of filamin A with RhoGDI2(Tyr153Glu).

Author information

1
Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA.
2
Faculty of Veterinary Medicine and Faculty of Biosciences and Pharmacy, University of Leipzig, Leipzig, Germany.
3
Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA. Electronic address: fnakamura@partners.org.

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.

KEYWORDS:

Filamin; Mechanotransduction; Phosphomimetic mutant; Phosphorylation; RhoGDI2; Src

PMID:
26707877
PMCID:
PMC4715983
DOI:
10.1016/j.bbrc.2015.12.044
[Indexed for MEDLINE]
Free PMC Article

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