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J Biol Chem. 2009 Apr 10;284(15):10202-10. doi: 10.1074/jbc.M807043200. Epub 2009 Feb 4.

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

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


Cell transformation by v-Src involves rearrangement of the actin cytoskeleton, disassembly of focal adhesions, and the development of anchorage-independent growth. Here, we report that this is dependent on annexin 2, a v-Src substrate and calcium-dependent regulator of actin dynamics. Using a thermoactivatable mutant of v-Src, we show that at the permissive temperature, annexin 2 becomes phosphorylated and colocalizes with activated v-Src and focal adhesion kinase both at the plasma membrane and in a Rab11-positive compartment of the endosomal pathway. In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. Our findings reveal a dual role for annexin 2, first as a regulator of v-Src trafficking and targeting and second as a v-Src effector in the reorganization of actin.

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