Disease relevance of Sorbs3

• Here, we show that vinexin beta increases the amount of and reduces the mobility on SDS-PAGE of Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE) 2 protein, which is a key factor modulating actin polymerization in migrating cells [1].

High impact information on Sorbs3

• When expressed, vinexin alpha and beta localized to focal adhesions in NIH 3T3 fibroblasts, and to cell-cell junctions in epithelial LLC-PK1 cells [2].
• Vinexin alpha also promoted upregulation of actin stress fiber formation [2].
• Furthermore, expression of vinexin increased focal adhesion size [2].
• Vinexin beta is a multiple SH3 motif-containing protein associated with the cytoskeleton and also present in the nucleus [3].
• We propose a model in which phosphorylation of the AF-1 domain controls RARgamma-mediated transcription through triggering the dissociation of vinexin beta [3].

Biological context of Sorbs3

• Using F9 cells stably overexpressing vinexin beta or vinexin knockdown by RNA interference, we demonstrate that vinexin beta is an inhibitor of RARgamma-mediated transcription [3].
• Vinexin, a recently identified cytoskeletal protein, contains three SH3 domains and plays important roles in regulation of cytoskeletal organization and signal transduction [4].
• To determine the role of Vinexin gamma during gonad formation, the gene was disrupted by targeted mutagenesis [5].
• Thus, Vinexin gamma seems to be implicated in regulation of Sox9 gene expression by modulating MAPK cascade in mouse fetal gonads [5].
• The phenotype displayed by the mice indicated that ERK activation was decreased in the Vinexin gamma(-/-) XY gonads, and Sox9 expression was down-regulated [5].

Anatomical context of Sorbs3

• Here, we show that exogenous expression of vinexin beta, a novel focal adhesion protein, allows anchorage-independent ERK2 activation stimulated by epidermal growth factor [6].
• Furthermore, we also found that vinexin alpha was expressed in the gonad and in a ventral part of the pons of 12.5 dpc embryos [4].
• Analysis of cryosections of 10.5 dpc embryos showed that vinexin alpha was expressed in a dorsal half of the retinal pigment epithelium and in the outflow tract and atrioventricular canal of the heart [4].
• In the present study, we identified a novel isoform of Vinexin, which is expressed in somatic cells but not germ cells of sexually indifferent stages of fetal gonads [5].
• In addition, we showed the colocalization between Vinexin alpha and SHIP2 at the periphery of transfected COS-7 cells [7].

Associations of Sorbs3 with chemical compounds

• Site-directed mutagenesis revealed that ERK2 mainly phosphorylated the serine 189 residue of vinexin beta [8].
• A mutational analysis identified tyrosine 127 on vinexin alpha as a major site of phosphorylation by c- or v-Abl [9].
• Vinexin beta interacts with the proline-rich region of WAVE2 through the first and second SH3 domains of vinexin beta [1].

Physical interactions of Sorbs3

• We report the identification of the cytoskeletal protein Vinexin as a protein interacting with SHIP2 [7].

Enzymatic interactions of Sorbs3

• We also found that vinexin alpha but not beta was phosphorylated at tyrosine residue when c-Abl or v-Abl was co-expressed [9].

Regulatory relationships of Sorbs3

• The dominant-negative mutant of vinexin beta inhibited the anchorage-independent ERK2 activation induced by the PKA inhibitor [6].
• Ultimately, Sox9 transcription was induced by Vinexin gamma [5].
• Our data suggest that SHIP2 interaction with Vinexin promotes the localization of SHIP2 at the periphery of the cells leaving its catalytic site intact [7].
• These results suggest that vinexin beta regulates the proteasome-dependent degradation of WAVE2 in a PKA-dependent manner [1].

Other interactions of Sorbs3

• We also show that the interaction with vinculin is necessary for the efficient localization of vinexin alpha and beta at focal adhesions [10].
• SHIP2 interaction with the cytoskeletal protein Vinexin [7].
• Mutations disrupting the interaction impaired the ability of vinexin beta to increase the amount of WAVE2 protein [1].

Analytical, diagnostic and therapeutic context of Sorbs3

• Using whole-mount in situ hybridization, we showed here that expression of vinexin alpha, the longer vinexin transcript, is strictly regulated, although the shorter transcript, vinexin beta, is expressed almost ubiquitously during embryonic development in mice [4].
• By Northern blotting, we identified two types of vinexin mRNA that were 3 and 2 kb in length [2].
• Whatever the final answer turns out to be, the genetic dissection of the SCAM superfamilies has led to a much better understanding of the different steps required to form, differentiate and modify a synapse [11].

References