Diaphanous-related formins bridge Rho GTPase and Src tyrosine kinase signaling

T Tominaga1, E Sahai, P Chardin

  • 1University of California, San Francisco Cancer Center 94115, USA.

Molecular Cell
|March 11, 2000
PubMed

Insights

Mouse Diaphanous-related formins (DRFs) like mDia1 and mDia2 are crucial for cell division and stress fiber formation. These proteins link Rho and Src signaling pathways, regulating cell structure and gene expression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Diaphanous-related formins (DRFs) are key regulators of the actin cytoskeleton.
  • DRFs are known to be involved in cell division and stress fiber formation.
  • The precise upstream regulators and signaling pathways involving DRFs are not fully understood.

Purpose of the Study:

  • To investigate the role of mouse DRFs, specifically mDia1 and mDia2, in cell regulation.
  • To elucidate the relationship between DRFs, Rho-kinase (ROCK), and Src tyrosine kinase in cellular processes.
  • To understand how DRFs integrate signals from Rho and Src.

Main Methods:

  • Utilized 'activated' variants of mDia1 and mDia2 lacking GTPase binding domains.
  • Co-expressed DRFs with Rho-kinase (ROCK) to study stress fiber formation.
  • Investigated the association and co-localization of Src tyrosine kinase with DRFs.
  • Assessed the impact of Src inhibition on DRF-mediated cellular processes.

Main Results:

  • Activated mDia1 and mDia2 cooperated with ROCK for stress fiber formation but activated SRF independently.
  • Src tyrosine kinase associated with and co-localized with DRFs in endosomes and mid-bodies.
  • Src inhibition blocked cytokinesis, SRF induction by activated DRFs, and stress fiber formation with ROCK.

Conclusions:

  • DRF proteins act as crucial coupling factors between Rho and Src signaling pathways.
  • DRFs play a significant role in regulating actin dynamics and cell division.
  • The interplay between DRFs, Rho, and Src is essential for coordinated cellular signaling and function.

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