Annexin A2 tyrosine phosphorylation induces cell scattering and branching morphogenesis via cofilin activation
نویسندگان
چکیده
Dynamic remodelling of the actin cytoskeleton is required for cell adhesion, motility and migration and can be regulated by tyrosine kinase activity. We identified phosphorylation of the lipid-, calcium-, and actin-binding protein, annexin A2 (AnxA2) at Tyr23 as a primary event preceding v-Src kinase-induced cell scattering and migration. Expression of the phospho-mimicking mutant, Y23E-AnxA2 was sufficient to induce actin reorganization and cell scattering. This was dependent on PI-3 kinase and MEK activity. RNAi-mediated knock-down of AnxA2 resulted in increased stress fiber formation and inhibition of cell scattering. In a 3D branching morphogenesis assay WT-AnxA2 cysts only developed branches in the presence of HGF while, Y23E-AnxA2 induced HGF-independent branching morphogenesis. The Y23E-AnxA2-induced morphology is associated with dephosphorylation/activation of the actin-severing protein, cofilin. Together our findings point to an important role for AnxA2 phosphorylation in the regulation of cytoskeletal dynamics during cell scattering and branching morphogenesis.
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