Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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WAS protein family member 2(WASF2) WAS protein family member 2(WASF2) Related Genes Homo sapiens
CHROMOSOME 1,
CYTOBAND 1p36.11-p34.3,
ENSEMBL_GENE_ID ENSG00000158195,
ENTREZ_GENE_ID 10163,
GENERIF_SUMMARY The WAVE2-Abi1-Nap1-PIR121 complex is as active as the WAVE2-Abi1 sub-complex in stimulating Arp2/3, and after Rac activation it is re-localized to the leading edge of ruffles in vivo., reconstitution of the Wave-2 complex and a study of the molecular architecture, Results suggest that phosphatidylinositol (3,4,5)-triphosphate recruits WAVE2 to the polarized membrane and that this recruitment is essential for lamellipodium formation at the leading edge., the 3 WAVE isoforms exhibit common and distinct features and may potentially be involved in the regulation of actin cytoskeleton in platelets, Abi-1-mediated coupling of Abl to WAVE2 promotes Abl-evoked WAVE2 tyrosine phosphorylation required to link WAVE2 with activated Rac and with actin polymerization and remodeling at the cell periphery., WAVE-2 and WAVE-3 expression was not changed by the megakaryocytic differentiation; WAVE-1 and WAVE-2 moved from a detergent-soluble cytosolic fraction to insoluble cytoskeleton fraction after platelet aggregation, WAVE2 is a key component of the actin regulatory machinery in T cells and that it also participates in linking intracellular calcium store depletion to calcium release-activated calcium (CRAC) channel activation., Coexpression of Arp2 and WAVE2 is correlated with poorer patient outcome., Therefore, IRSp53 optimizes the activity of the WAVE2 complex in the presence of activated Rac and PIP(3)., c-Abl activates WAVE2 via tyrosine phosphorylation to promote actin remodeling in vivo; Abi-1 forms the crucial link between these two factors, WAVE2 expression is elevated in HCC tissues, which correlates with a poor prognosis, suggesting WAVE2 as a candidate prognostic marker of HCC., Colocalization of Arp2 and WAVE2 is an independent risk factor for liver metastasis of colorectal carcinoma., Data show that Chlamydia trachomatis activates Rac and promotes its interaction with WAVE2 and Abi-1 to activate the Arp2/3 complex resulting in the induction of actin cytoskeletal rearrangements that are required for invasion., 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., Over-expression of WAVE2 is seen in node-positive cases as well as in moderately and poorly differentiated breast cancers., Data suggest that the promotion of lamellipodia formation by HGF in MDA-MB-231 cells is Rac1-dependent and requires KIF5B-mediated transport of WAVE2 and IQGAP1 to the cell periphery along microtubules., results suggest that long protrusions formed in a WAVE2- and microtubule-dependent manner may identify the cells at the later stage of invasion, possibly after the formation of invadopodia in the 3-D cultures, Results identify a mechanism by which the WAVE2 complex regulates T cell receptor signaling to Rap1 and integrin activation via Abl- and CrkL-C3G., Phosphorylation of all five sites on endogenous WAVE2 and their mutation to non-phosphorylatable alanine residues leads to inhibition of WAVE2 function in vivo, was demonstrated., Pak1 protein binds to WASF2 protein and is transported with WASF2 protein to the leading edge by stimulation with hepatocyte growth factor., betaPIX and GIT1 regulate the hepatocyte growth factor-induced and Rac1-dependent membrane transport of WAVE2 and consequently, lamellipodia formation., HSPC300 is associated with metastatic potential of lung squamous cell carcinoma through its interaction with WAVE2, Data show that activation of the WAVE2 complex requires simultaneous interactions with prenylated Rac-GTP and acidic phospholipids, as well as a specific state of phosphorylation., WAVE2-membrane targeting is directionally controlled by binding of the EB1-stathmin complex to WAVE2-bearing microtubules and by the interaction between WAVE2 and PIP3 produced near IGF-IR that is locally activated by IGF-I., WAVE2 complexs with insulin receptor substrate p53 and is crucial for membrane targeting followed by local accumulation of WAVE2 at the leading edge of cells., WAVE2 works as an A-kinase-anchoring protein that recruits PKA at membrane protrusions and plays a role in the enlargement of membrane protrusions induced by PKA activation, MYH9 is required for lamellipodia formation since it provides contractile forces and tension for the F-actin network to form convex arcs at the leading edge through constitutive binding to WAVE2 and colocalization with PIP(3) in response to IGF-I., WAVE2 and WASp define parallel pathways to F-actin reorganization and function in NK cells; although WAVE2 was not required for NK cell innate function, it was accessible through adaptive immunity via IL-2., Data suggest that ERK coordinates adhesion disassembly with WAVE2 regulatory complex activation and actin polymerization to promote productive leading edge advancement during cell migration., results indicate that by mediating intensive F-actin accumulation at the sites of cell infiltration, WAVE2, N-WASP, and Mena are crucial for PI3K-dependent cell invasion induced by PDGF, We demonstrate that WAVE2-Arp2/3 is a major nucleator of actin assembly at the zonula adherens and likely acts in response to junctional Rac signaling, results suggest that SKAP2 negatively regulates cell migration and tumor invasion in fibroblasts and glioblastoma cells by suppressing actin assembly induced by the WAVE2-cortactin complex, Identification of an onco-suppressive role of miR-146a in gastric cancer cells by its reduction of WASF2 expression., data reveal a critical role for WAVE2 complex in regulation of cellular signaling and epithelial morphogenesis, Decreased expression of Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2 may be involved in the development of pre-eclampsia., these results suggest that Arp2/3 and the upstream regulator, WAVE2, are essential co-factors hijacked by HIV for intracellular migration, and may serve as novel targets to prevent HIV transmission., Cortactin has a role as a scaffold for Arp2/3 and WAVE2 at the epithelial zonula adherens, WAVE2 is down-regulated in gastric cancer, WASp and WAVE2 differ in their dynamics and their associated proteins, the MCP1-induced cortactin phosphorylation is dependent on PLCb3-mediated PKC activation, and siRNA-mediated down-regulation of either of these molecules prevents cortactin interaction with WAVE2,
SP_COMMENT domain:Binds the Arp2/3 complex through the C-terminal region and actin through verprolin homology (VPH) domain., function:Downstream effector molecules involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton., similarity:Belongs to the SCAR/WAVE family., similarity:Contains 1 WH2 domain., subcellular location:At the interface between the lamellipodial actin meshwork and the membrane., subunit:Binds actin and the Arp2/3 complex. Interacts with BAIAP2. Component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1, NCKAP1/NAP1 and WASF2/WAVE2. Directly interacts with C3orf10/HSPC300., tissue specificity:Expressed in all tissues with strongest expression in placenta, lung, and peripheral blood leukocytes, but not in skeletal muscle.,