PKA and PKGIndependent Phosphorylation of EnaVASP Proteins

In addition to PKA and PKG, PKC has also been reported to phosphorylate VASP at the Ser157 site. Chitaley et al. (2004) reported PKA- and PKG-independent phosphorylation of Ser157, but not Ser239, in cultured rat smooth muscle cells from the aorta. PKC appeared to be the kinase responsible for this post-translational modification, since phosphorylation was induced by phorbol 12-myristate 13-acetate (PMA) and inhibited by specific PKC inhibition. Moreover, Chitaley et al. (2004) showed that recombinant PKCa directly phosphorylated VASP at the residue Ser157. Wentworth et al. (2006) also showed PKC-dependent Ser157 phosphoryla-tion of VASP. These authors reported PMA-dependent phosphorylation of VASP Ser157 in human platelets and inhibition of it by bisindolylmaleimide I (BIM I), a specific PKC inhibitor. Moreover, the activation of platelets by thrombin, a physiological platelet agonist, induced VASP Ser157 phosphorylation, which was partially PKC dependent. Finally, Pula et al. (2006) reported negative regulation of VASP Ser157 phosphorylation by PKC5. The molecular mechanism of this regulation of VASP phosphorylation is not entirely clear, but it does not involve the control of PKA or PKG activity.

Finally, in contrast to the other members of the family, Mena is tyrosine-phosphorylated (Gertler et al. 1996). Ena, the Drosophila ortholog of Mena, is tyrosine-phosphorylated by Abelson tyrosine kinase (Comer et al. 1998). Subsequently, Mena has also been reported to be phosphorylated by c-Abl kinase at the residue Tyr296, with Abi-1 (Abl interactor 1) binding to Mena and dramatically enhancing its tyrosine phosphorylation by c-Abl (Tani et al. 2003).

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