cAMP-dependent Protein Kinase Phosphorylation of EVL, a Mena/VASP Relative, Regulates Its Interaction with Actin and SH3 Domains
pmid: 10945997
cAMP-dependent Protein Kinase Phosphorylation of EVL, a Mena/VASP Relative, Regulates Its Interaction with Actin and SH3 Domains
Proteins of the Ena/VASP family are implicated in processes that require dynamic actin remodeling such as axon guidance and platelet activation. In this work, we explored some of the pathways that likely regulate actin dynamics in part via EVL (Ena/VASP-like protein). Two isoforms, EVL and EVL-I, were highly expressed in hematopoietic cells of thymus and spleen. In CD3-activated T-cells, EVL was found in F-actin-rich patches and at the distal tips of the microspikes that formed on the activated side of the T-cells. Like the other family members, EVL localized to focal adhesions and the leading edge of lamellipodia when expressed in fibroblasts. EVL was a substrate for the cAMP-dependent protein kinase, and this phosphorylation regulated several of the interactions between EVL and its ligands. Unlike VASP, EVL nucleated actin polymerization under physiological conditions, whereas phosphorylation of both EVL and VASP decreased their nucleating activity. EVL bound directly to the Abl, Lyn, and nSrc SH3 domains; the FE65 WW domain; and profilin, likely via its proline-rich core. Binding of Abl and nSrc SH3 domains, but not profilin or other SH3 domains, was abolished by cAMP-dependent protein kinase phosphorylation of EVL. We show strong cooperative binding of two profilin dimers on the polyproline sequence of EVL. Additionally, profilin competed with the SH3 domains for binding to partially overlapping binding sites. These data suggest that the function of EVL could be modulated in a complex manner by its interactions with multiple ligands and through phosphorylation by cyclic nucleotide dependent kinases.
- Ghent University Belgium
- Massachusetts Institute of Technology United States
CD4-Positive T-Lymphocytes, Microfilament Proteins, Molecular Sequence Data, Fluorescent Antibody Technique, Fibroblasts, Lymphocyte Activation, Phosphoproteins, Binding, Competitive, Cyclic AMP-Dependent Protein Kinases, Actins, Cytoskeletal Proteins, Mice, Biopolymers, Contractile Proteins, Animals, Amino Acid Sequence, Phosphorylation, Carrier Proteins, Cell Adhesion Molecules, Cells, Cultured
CD4-Positive T-Lymphocytes, Microfilament Proteins, Molecular Sequence Data, Fluorescent Antibody Technique, Fibroblasts, Lymphocyte Activation, Phosphoproteins, Binding, Competitive, Cyclic AMP-Dependent Protein Kinases, Actins, Cytoskeletal Proteins, Mice, Biopolymers, Contractile Proteins, Animals, Amino Acid Sequence, Phosphorylation, Carrier Proteins, Cell Adhesion Molecules, Cells, Cultured
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