The mammalian formin FHOD1 is activated through phosphorylation by ROCK and mediates thrombin-induced stress fibre formation in endothelial cells

Ryu Takeya, Kenichiro Taniguchi, Shuh Narumiya, Hideki Sumimoto

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Formin-family proteins, in the active state, form actin-based structures such as stress fibres. Their activation mechanisms, however, are largely unknown except that mDia and its closely related formins can be activated by direct binding of the small GTPase Rho or Cdc42. Here we show that the Rho-dependent protein kinase ROCK phosphorylates the C-terminal residues Ser1131, Ser1137, and Thr1141 of formin homology domain protein 1 (FHOD1), a major endothelial formin that is normally autoinhibited by intramolecular interaction between the N- and C-terminal regions. Phosphorylation of FHOD1 at the three residues fully disrupts the autoinhibitory interaction, which culminates in formation of stress fibres. We also demonstrate that, in vascular endothelial cells, thrombin, a vasoactive substance leading to Rho activation, elicits both FHOD1 phosphorylation and stress fibre formation in a ROCK-dependent manner, and that FHOD1 depletion by RNA interference impairs thrombin-induced stress fibre formation. Based on these findings we propose a novel mechanism for activation of formin-family proteins: ROCK, activated by G protein-coupled receptor ligands such as thrombin, directly phosphorylates FHOD1 at the C-terminal region, which renders this formin in the active form, leading to stress fibre formation.

Original languageEnglish
Pages (from-to)618-628
Number of pages11
JournalEMBO Journal
Volume27
Issue number4
DOIs
Publication statusPublished - Feb 20 2008

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Stress Fibers
Phosphorylation
Endothelial cells
Thrombin
Endothelial Cells
Fibers
Proteins
Chemical activation
rho-Associated Kinases
Monomeric GTP-Binding Proteins
G-Protein-Coupled Receptors
RNA Interference
Actins
Protein Domains
Ligands
RNA

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

Cite this

The mammalian formin FHOD1 is activated through phosphorylation by ROCK and mediates thrombin-induced stress fibre formation in endothelial cells. / Takeya, Ryu; Taniguchi, Kenichiro; Narumiya, Shuh; Sumimoto, Hideki.

In: EMBO Journal, Vol. 27, No. 4, 20.02.2008, p. 618-628.

Research output: Contribution to journalArticle

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