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Annexin 2 has a dual role as regulator and effector of v-Src in cell transformation

Matthew J Hayes1, Stephen E Moss

  • 1Division of Cell Biology, University College London Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, United Kingdom.

The Journal of Biological Chemistry
|February 6, 2009
PubMed

Insights

Annexin 2 is crucial for v-Src-mediated cell transformation by regulating v-Src trafficking and actin reorganization. Depleting annexin 2 prevents cell transformation, highlighting its dual role.

Area of Science:

  • Cell Biology
  • Molecular Oncology

Background:

  • v-Src oncogene drives cell transformation through actin cytoskeleton rearrangement and focal adhesion disassembly.
  • Annexin 2 is a known substrate of v-Src and regulates actin dynamics.

Purpose of the Study:

  • To investigate the role of annexin 2 in v-Src-induced cell transformation.
  • To elucidate the molecular mechanisms by which annexin 2 mediates v-Src effects.

Main Methods:

  • Utilized a thermoactivatable v-Src mutant to study its effects at permissive temperatures.
  • Employed small interfering RNA (siRNA) to deplete annexin 2 levels.
  • Investigated protein localization and colocalization using microscopy.
  • Assessed cell transformation and anchorage-independent growth.

Main Results:

  • Phosphorylation and colocalization of annexin 2 with activated v-Src and focal adhesion kinase were observed at the plasma membrane and in endosomes.
  • Annexin 2 depletion prevented v-Src targeting to the plasma membrane and perinuclear vesicles.
  • Cells depleted of annexin 2 did not undergo transformation despite v-Src activation.
  • Annexin 2 demonstrated a dual role in regulating v-Src trafficking and actin reorganization.

Conclusions:

  • Annexin 2 is essential for v-Src-mediated cell transformation.
  • Annexin 2 acts as a critical regulator of v-Src trafficking and localization.
  • Annexin 2 functions as a v-Src effector in actin cytoskeleton remodeling.

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