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Unc73 is a homolog of mammalian Trio. The Unc73 Rac-GEF domain activates the Rac GTPase in vitro and stimulates actin polymerization when expressed in rat fibroblasts. In addition, expression of a truncated form of Unc73 that lacks the Rho-GEF activity is shown to rescue axon guidance defects in Unc73 mutants.
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A novel proline-rich motif present in ActA of Listeria monocytogenes and cytoskeletal proteins is the ligand for the EVH1 domain, a protein module present in the Ena/VASP family
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•], this paper demonstrates that EVH1 domains are structurally similar to pleckstrin homology and phosphotyrosine binding domains. Despite the similarities, these domains bind to distinct peptide and/or phospholipid ligands. The fact that the EVH1 domains resembles pleckstrin homology domains suggests that EVH1 association with the membrane could play a role in Ena/VASP protein localization.
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•], this paper demonstrates that EVH1 domains are structurally similar to pleckstrin homology and phosphotyrosine binding domains. Despite the similarities, these domains bind to distinct peptide and/or phospholipid ligands. The fact that the EVH1 domains resembles pleckstrin homology domains suggests that EVH1 association with the membrane could play a role in Ena/VASP protein localization.
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Mutations in Drosophila enabled and rescue by human vasodilator-stimulated phosphoprotein (VASP) indicate important functional roles for Ena/VASP homology domain 1 (EVH1) and EVH2 domains
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Mutations in two the Ena alleles were mapped to the EVH1 and EVH2 domains and were shown to impair Ena function in vivo, suggesting that EVH1-mediated localization and EVH2-mediated oligomerization are both required for proper Ena function. In addition, VASP was shown to rescue the embryonic lethality associated with loss of Ena function, indicating that vertebrate VASP can functionally substitute for Ena.
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Enabled, a dosage-sensitive suppressor of mutations in the Drosophila Abl tyrosine kinase, encodes an Abl substrate with SH3 domain-binding properties
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The authors map the major D-abl tyrosine phosphorylation sites on Ena by expressing Ena in Drosophila S2 culture cells, and they show that Ena phosphorylation by D-abl modulates in vitro binding of Ena to the Abl SH3 domain.
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Comer A.R., Ahern-Djamali S.M., Juang J.L., Jackson P.D., Hoffmann F.M. Phosphorylation of Enabled by the Drosophila Abelson tyrosine kinase regulates the in vivo function and protein-protein interactions of Enabled. Mol Cell Biol. 18:1998;152-160. The authors map the major D-abl tyrosine phosphorylation sites on Ena by expressing Ena in Drosophila S2 culture cells, and they show that Ena phosphorylation by D-abl modulates in vitro binding of Ena to the Abl SH3 domain.
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Mena is required for neurulation and commissure formation
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Mena is highly enriched in the tips of growth cone filopodia and appears to play an important role in commissural axon guidance. Mena mutants are sensitive to a reduction in the amount of profilin, suggesting an important functional role for Mena in regulation of the actin cytoskeleton.
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Lanier L.M., Gates M.A., Witke W., Menzies A.S., Wehman A.M., Macklis J.D., Kwiatkowski D., Soriano P., Gertler F.B. Mena is required for neurulation and commissure formation. Neuron. 22:1999;313-325. Mena is highly enriched in the tips of growth cone filopodia and appears to play an important role in commissural axon guidance. Mena mutants are sensitive to a reduction in the amount of profilin, suggesting an important functional role for Mena in regulation of the actin cytoskeleton.
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The vasodilator-stimulated phosphoprotein (VASP) is involved in cGMP- And cAMP-mediated inhibition of agonist-induced platelet aggregation, but is dispensable for smooth muscle function
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