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GIT2 represses Crk- and Rac1-regulated cell spreading and Cdc42-mediated focal adhesion turnover

Scott R Frank1, Molly R Adelstein, Steen H Hansen

  • 1Boston Biomedical Research Institute, Watertown, MA 02115, USA.

The EMBO Journal
|April 22, 2006
PubMed

Insights

G protein-coupled receptor kinase interactor 2 (GIT2) represses cell motility by inhibiting lamellipodial extension and focal adhesion turnover. Loss of GIT2 function is necessary for cell migration, suggesting it

Area of Science:

  • Cell biology
  • Molecular and cell signaling
  • Cancer research

Background:

  • G protein-coupled receptor kinase interactors (GITs) are known regulators of focal adhesion (FA) turnover, cell spreading, and motility.
  • GITs interact with paxillin and the Rac-exchange factor Pak-interacting exchange factor beta (betaPIX).
  • The specific roles of GIT proteins, particularly GIT1 and GIT2, in regulating cell motility remain unclear.

Purpose of the Study:

  • To elucidate the distinct roles of GIT1 and GIT2 in cell motility.
  • To determine whether GITs activate or repress cell migration.
  • To identify the molecular mechanisms by which GITs regulate cell movement.

Main Methods:

  • Knockdown of endogenous GIT2 using RNA interference.
  • Analysis of lamellipodial extension and focal adhesion turnover.
  • Investigation of Rac1 and Cdc42 signaling pathways.
  • Assessment of cell migration in MCF10A cells.
  • Examination of the interaction between GIT2 and the adaptor protein Crk.

Main Results:

  • Endogenous GIT2 is essential for repressing lamellipodial extension and FA turnover.
  • GIT2 inhibits Rac1- and Cdc42-dependent signaling pathways.
  • The adaptor protein Crk is a key target of GIT2 inhibition.
  • betaPIX is dispensable for the effects of GIT2 knockdown.
  • Loss of GIT2 function is sufficient to induce migration in MCF10A cells.

Conclusions:

  • GIT2 plays a critical role in repressing cell motility.
  • Inactivation of GIT2 is a prerequisite for initiating cell migration.
  • GIT2 may be a target of oncogenic pathways that promote cell migration.

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