Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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vinculin(VCL) vinculin(VCL) Related Genes Homo sapiens
CYTOBAND 10q22.2,
GENERIF_SUMMARY Here, we report on a transient interaction between the lipid-dependent protein kinase Calpha and vinculin, an early component of these sites, during spreading of HeLa cells on collagen, crystal structures of human vinculin in its inactive and talin-activated states, Findings support a model in which talin binds to and activates multiple vinculin molecules to provoke rapid reorganization of the actin cytoskeleton., vinculin is tyrosine phosphorylated in platelets spread on fibrinogen, and the phosphorylation is Src kinases dependent, immunohistochemistry of vinculin in alpha- and gamma-sarcoglycanopathy, two head-tail interfaces cooperate to suppress activation of vinculin by talin, Beyond providing direct evidence that vinculin is activated at focal adhesions, this study shows that the specific functional conformation correlates with regional cellular dynamics., A model is suggested where vinculin's Vh1 domain acts as a molecular switch that undergoes distinct structural changes provoked by talin and alpha-actinin binding in focal adhesions versus adherens junctions, respectively., Same fundamental metavinculin mutation can yield either hypertrophic or dilated cardiomyopathic phenotype, underscoring a critical role for modifier genes and/or environmental stressors in cardiac remodeling., vinculin binding to talin depends on stability of the helical bundles that make up the talin rod, vinculin conformation, as modulated by the strength of HTI, directly regulates the formation and lifetime of talin-vinculin complexes in cells, a vinculin missense mutation confers susceptibility to hypertrophic cardiomyopathy, Vinculin is activated by virulence factor of Shigella flexneri., cardiac hypertrophy may be associated with different expression of the marker vinculin/metavinculin depending on the underlying pathophysiology, Invasin IpaA subverts vinculin's functions. Shigella flexneri utilizes a remarkable level of molecular mimicry of the talin-vinculin interaction to activate vinculin., Results decribe a mechanism in which signals from the T cell receptor produce WAVE2-ARP2/3-mediated de novo actin polymerization, leading to integrin clustering and high-affinity binding through the recruitment of vinculin and talin., vinculin plays a role in growth regulation of neuroendocrine tumors and in expression of CLD4, analysis of vinculin binding in its closed conformation by a helix addition mechanism, alpha-synemin, but not beta-synemin, interacts with both vinculin and metavinculin, The expression of vinculin constructs with unmasked binding sites in the head and tail regions induces dramatic focal adhesion growth, which is mediated by their direct interaction with talin., A subset of the tumor-specific splicing alterations (ACTN1, CALD1, and VCL) was found in all three organs and may represent general cancer-related splicing events., The structural and biochemical properties of the last 21 residues of the vinculin tail domain were investigated., Vinculin has a similar staining pattern in liver as CRBP-1 but additionally stains SMCs, and (myo)fibroblasts., the vinculin-talin-integrin system have a role in the transduction of mechanical force to the extracellular matrix, Experiments on a nonphosphorylatable vinculin mutant construct at phosphorylation site tyr1065 confirmed the direct interplay between phosphorylation and exchange dynamics of adhesion proteins during adhesion site maturation., Focal adhesion kinase expression reduced vinculin localization to focal adhesions by 35% independently of changes in integrin binding and localization of talin and paxillin., This review discusses the general function of vinculin/metavinulin as well as talin 1 and talin 2, with emphasis on what is understood about their role in the cardiac myocyte and in whole heart., an interaction between beta-catenin and vinculin is crucial for stabilizing E-cadherin at the cell surface, A helix replacement mechanism directs metavinculin's unique functions., The data identify the kidney as a new organ site for ALK-associated carcinomas and VCL as a novel ALK fusion partner., VCL is expressed differently in benign prostatic hyperplasia and prostate cancer, which may serve as an indicator for the differential diagnosis of benign and malignant prostate diseases., When myosin II contractility was inhibited, the k(off) values for all three proteins changed rapidly, in a highly protein-specific manner, IpaA-directed mimicry of talin in activating vinculin occurs through three high affinity VBSs that are essential for Shigella pathogenesis., Talin-1 and vinculin negatively affect tyrosine phosphorylation of paxillin, a novel positive regulator of HIV-1 infection, and impose an early block to infection by distinct retroviruses., sca4 activates vinculin and interacts with the actin cytoskeleton; vinculin has roles in Rickettsia pathogenesis, alpha-catenin employs a novel mechanism to activate vinculin and may explain how vinculin is differentially recruited and/or activated in cell-cell and cell-matrix adhesions., Data show that SGK1 regulates cell migration via vinculin dephosphorylation, a mechanism that is controlled by membrane androgen receptor function., Results implicate Vinculin-dependent VE-cadherin mechanosensing in endothelial processes such as leukocyte extravasation and angiogenesis., binding studies suggest that vinculin must be in an activated state to bind to alpha-catenin and that this interaction is stabilized by the formation of a ternary alpha-catenin-vinculin-F-actin complex, which can be formed via the F-actin binding domain, The metavinculin promoted severing of actin filaments, most efficiently at substoichiometric concentrations., These binding assays show that raver1 forms a ternary complex with metavinculin and vinculin mRNA., Western blotting demonstrated that vinculin was predominantly expressed in the pancreatic cancer tissues compared with non-cancerous tissues; findings indicate that vinculin may be a clinically useful biomarker of pancreatic cancer, these data suggest that metavinculin enrichment in attachment sites of muscle cells leads to higher mechanical stability of adhesion complexes allowing for greater shear force resistance., Data indicate that lasp-2 interacts with the focal adhesion proteins vinculin and paxillin., Studies indicate that that vinculin not only bundles actin filaments but can also cap these filaments and promote actin polymerization., Vinculin protein level in SW620 was much higher than that in SW480 cells., VAX1 rs10787760, rs6585429 and rs1871345 polymorphisms may be involved in nonsyndromic cleft lip with or without cleft palate in Brazilian patients, but there is no association with polymorphisms in FGF12, VCL, or CX43, this study elucidated how tensile forces generated by single stress fibers are temporally and spatially distributed to vinculin mechanosensors located within cell-matrix adhesions, p38 mitogen-activated protein kinase interacts with vinculin at focal adhesions during fatty acid-stimulated cell adhesion., Vinculin is a new marker for atherosclerosis., Data indicate the role of vinculin in inducing the talin mediated integrin activation., The activation of vinculin by stretched talin induces a positive feedback that reinforces the actin-talin-vinculin association., These results indicate that mechanical forces loaded to focal adhesions (FAs) facilitate vinculin binding to talin at FAs., vinculin binds to Rab5 and is required for Staphylococcus aureus uptake in cells., Case Report, These data reveal an unexpected regulatory mechanism in which vinculin Y822 phosphorylation determines whether cadherins transmit force and provides a paradigm for how a shared component of adhesions can produce biologically distinct functions., Our NMR and ITC data indicate that the SH3a and SH3b domains of CAP simultaneously bind to a long proline-rich region of vinculin with different binding specificities, Vinculin was identified as a potential plasma biomarker for age-related macular degeneration., vinculin negatively regulates malignant phenotype of tumor cells including MT1-MMP transcription through MEK/ERK pathway, PIP2 binding is required for the control of vinculin dynamics and turnover in focal adhesions., Vinculin expression was found to be significantly downregulated., vinculin, present in the joints of anti-citrullinated protein antibody (ACPA)(+) rheumatoid arthritis patients, was identified as an autoantigen targeted by ACPA and CD4(+) T cells., Analysis showed that ITGB4 and VCL were upregulated in exosomes derived from taxane-resistant prostate cancer cells suggesting them as useful markers for progression of prostate cancer associated with taxane-resistance., Data indicate that specific protein interactions are spatially segregated within focal adhesions (FAs) at the nanoscale to regulate vinculin activation and function., This study defined a plastic relationship between vinculin-mediated tension and adhesion complex area that controls fundamental cell-matrix adhesion properties., The VCL-encoding protein was involved in cardiomyopathy that associated with hypertension, therefore our results suggest the rs4746172 of VCL may be a novel target for clinical interventions to reduce CVD risk by regulating blood pressure in male Chinese, Upon actin engagement, the N-terminal "strap" and helix 1 are displaced from the vinculin tail helical bundle to mediate actin bundling., Three novel genes were identified as recurrently mutated; MYCN, MYO5B and VCL, and mutations in these genes were exclusively found in malignant sympathetic paraganglioma tumors., roles and mechanisms of phospholipids in regulating the structure and function of vinculin and of its muscle-specific metavinculin splice variant.,
OMIM_DISEASE Cardiomyopathy, dilated, 1W, Cardiomyopathy, hypertrophic, 15,
SP_COMMENT disease:Defects in VCL are the cause of cardiomyopathy dilated type 1W (CMD1W) [MIM:611407]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death., function:Involved in cell adhesion. May be involved in the attachment of the actin-based microfilaments to the plasma membrane. May also play important roles in cell morphology and locomotion., online information:Vinculin entry, PTM:Aceylated; mainly by myristic acid but also small amount of palmitic acid., PTM:Phosphorylated; on serines, threonines and tyrosines. Phosphorylation on Tyr-1133 in activated platelets affects head-tail interactions and cell spreading but has no effect on actin binding nor on localization to focal adhesion plaques., similarity:Belongs to the vinculin/alpha-catenin family., subcellular location:Cytoplasmic face of adhesion plaques., subunit:Exhibits self-association properties. Interacts with NRAP and SORBS1 (By similarity). Interacts with TLN1. Interacts with SYNM., tissue specificity:Metavinculin is muscle-specific.,