PMID:14614988

Citation	Karnik, SK, Wythe, JD, Sorensen, L, Brooke, BS, Urness, LD and Li, DY (2003) Elastin induces myofibrillogenesis via a specific domain, VGVAPG. Matrix Biol. 22:409-25
Abstract	A hallmark of vascular smooth muscle cells (VSMCs) is their dynamic ability to assemble and disassemble contractile proteins into sarcomeric units depending upon their phenotypic state. This phenotypic plasticity plays an important role during vascular development and in obstructive vascular disease. Previously, we showed that the Elastin gene product, tropoelastin, activates myofibrillar organization of VSMCs. Recently, others have suggested that elastin does not have a direct signaling role but rather binds to and alters the interactions of other matrix proteins with their cognate receptors or disrupts the binding of growth factors and cytokines. In contrast, we provide evidence that tropoelastin directly regulates contractile organization of VSMCs. First, we show that a discrete domain within tropoelastin, VGVAPG, induces myofibrillogenesis in a time- and dose-dependent fashion. We confirm specificity using a closely related control peptide that fails to stimulate actin stress fiber formation. Second, the activity of VGVAPG is not affected by the presence or absence of other serum or matrix components. Third, both the elastin hexapeptide and tropoelastin stimulate actin polymerization through a common pertussis toxin-sensitive G protein pathway that activates RhoA-GTPase and results in the conversion of G to F actin. Collectively, these data support a model whereby the elastin gene product, signaling through the VGVAPG domain, directly induces VSMC myofibrillogenesis.
Links	PubMed
Keywords	Actins/chemistry; Animals; Blotting, Western; Cell Line; Cell Movement; Chemotaxis; Cyclic AMP/metabolism; Cytoplasm/metabolism; Densitometry; Dose-Response Relationship, Drug; Elastin/chemistry; Elastin/metabolism; Fluorescent Antibody Technique, Indirect; Intracellular Signaling Peptides and Proteins; Mice; Mice, Transgenic; Microscopy, Electron; Microscopy, Fluorescence; Muscle, Smooth, Vascular/cytology; Myocytes, Smooth Muscle/metabolism; Peptides/chemistry; Pertussis Toxin/pharmacology; Phenotype; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases/metabolism; Time Factors; Tropoelastin/chemistry; Vinculin/chemistry; rho-Associated Kinases
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