Vav protein family members are multiple domain proteins, including Vav from flies and Vav1/2/3 from mammals. They have a calponin homology (CH) domain, an acidic domain (AC), a Dbl homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich (CR) domain containing a zinc finger, and a compound domain having SH2 and SH3 domains. Therefore they may participate in the activity of several pathways [, ]. They are signal transducer proteins that couple tyrosine kinase signals with the activation of the Rho/Rac GTPases, [, , ]. This entry includes mammalian Vav1 and its homologues.
VAV1 (also known as proto-oncogene vav) is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells [, , ]. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization [, ]. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others []. The VAV protein family members are multiple domain proteins, including Vav from flies and VAV1/2/3 from mammals. VAV1 predominates in hematopoietic cells, whereas VAV2 and VAV3 are more broadly expressed. They have a calponin homology (CH) domain, an acidic domain (AC), a Dbl homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich (CR) domain containing a zinc finger, and a complex region with SH2 and SH3 domains. Therefore they may participate in the activity of several pathways [, ]. They are signal transducer proteins that couple tyrosine kinase signals with the activation of the Rho/Rac GTPases, [, , ]. This entry represents the second SH3 domain of VAV1. This domain interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2 [].
VAV1 (also known as proto-oncogene vav) is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells [, , ]. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization [, ]. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others []. The VAV protein family members are multiple domain proteins, including Vav from flies and VAV1/2/3 from mammals. VAV1 predominates in hematopoietic cells, whereas VAV2 and VAV3 are more broadly expressed. They have a calponin homology (CH) domain, an acidic domain (AC), a Dbl homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich (CR) domain containing a zinc finger, and a complex region with SH2 and SH3 domains. Therefore they may participate in the activity of several pathways [, ]. They are signal transducer proteins that couple tyrosine kinase signals with the activation of the Rho/Rac GTPases, [, , ]. This entry represents the first SH3 domain of VAV1.
This entry represents the SH2 domain of VAV1 from vertebrates.VAV1 (also known as proto-oncogene vav) is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells [, , ]. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization [, ]. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others []. The VAV protein family members are multiple domain proteins, including Vav from flies and VAV1/2/3 from mammals. VAV1 predominates in hematopoietic cells, whereas VAV2 and VAV3 are more broadly expressed. They have a calponin homology (CH) domain, an acidic domain (AC), a Dbl homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich (CR) domain containing a zinc finger, and a complex region with SH2 and SH3 domains. Therefore they may participate in the activity of several pathways [, ]. They are signal transducer proteins that couple tyrosine kinase signals with the activation of the Rho/Rac GTPases, [, , ].
This entry represents the SH2 domain of VAV2, which is a member of the VAV family. The SH2 domain of VAV2 has been shown to interact with PPxY motifs of TXNIP (thioredoxin-interacting protein) []. The VAV protein family members are multiple domain proteins, including Vav from flies and VAV1/2/3 from mammals. VAV1 predominates in hematopoietic cells, whereas VAV2 and VAV3 are more broadly expressed. They have a calponin homology (CH) domain, an acidic domain (AC), a Dbl homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich (CR) domain containing a zinc finger, and a complex region with SH2 and SH3 domains. Therefore they may participate in the activity of several pathways [, ]. They are signal transducer proteins that couple tyrosine kinase signals with the activation of the Rho/Rac GTPases, [, , ].
This entry represents the SH2 domain of VAV3, which belongs to the VAV family. VAV3 is involved in the regulation of osteoclast function []and in central nervous system development and plasticity [].The VAV protein family members are multiple domain proteins, including Vav from flies and VAV1/2/3 from mammals. VAV1 predominates in hematopoietic cells, whereas VAV2 and VAV3 are more broadly expressed. They have a calponin homology (CH) domain, an acidic domain (AC), a Dbl homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich (CR) domain containing a zinc finger, and a complex region with SH2 and SH3 domains. Therefore they may participate in the activity of several pathways [, ]. They are signal transducer proteins that couple tyrosine kinase signals with the activation of the Rho/Rac GTPases, [, , ].
The adaptor protein 3BP2/SH3BP2 is a cytoplasmic adaptor that contributes to the regulation of immune responses []. The protein-tyrosine kinase Syk phosphorylates 3BP2 which results in the activation of Rac1 through the interaction with the SH2 domain of Vav1 and induces the binding to the SH2 domain of the upstream protein-tyrosine kinase Lyn and enhances its kinase activity []. 3BP2 has a positive regulatory role in IgE-mediated mast cell activation []. In lymphocytes, engagement of T cell or B cell receptors triggers tyrosine phosphorylation of 3BP2 []. 3BP2 is required for the proliferation of B cells and B cell receptor signaling. Mutations in the 3BP2 gene are responsible for cherubism resulting in excessive bone resorption in the jaw [].This entry represents the SH2 domain of SH3BP2.
The adaptor protein 3BP2/SH3BP2 is a cytoplasmic adaptor that contributes to the regulation of immune responses []. The protein-tyrosine kinase Syk phosphorylates 3BP2 which results in the activation of Rac1 through the interaction with the SH2 domain of Vav1 and induces the binding to the SH2 domain of the upstream protein-tyrosine kinase Lyn and enhances its kinase activity []. 3BP2 has a positive regulatory role in IgE-mediated mast cell activation []. In lymphocytes, engagement of T cell or B cell receptors triggers tyrosine phosphorylation of 3BP2 []. 3BP2 is required for the proliferation of B cells and B cell receptor signaling. Mutations in the 3BP2 gene are responsible for cherubism resulting in excessive bone resorption in the jaw [].
Vav acts as a guanosine nucleotide exchange factor (GEF) for Rho/Rac proteins. They control processes including T cell activation, phagocytosis, and migration of cells. The Vav subgroup of Dbl GEFs consists of three family members (Vav1, Vav2, and Vav3) in mammals []. Vav1 is preferentially expressed in the hematopoietic system, while Vav2 and Vav3 are described by broader expression patterns []. Mammalian Vav proteins consist of a calponin homology (CH) domain, an acidic region, a catalytic Dbl homology (DH) domain, a PH domain, a zinc finger cysteine rich domain (C1/CRD), and an SH2 domain, flanked by two SH3 domains. In invertebrates such as Drosophila and C. elegans, Vav is missing the N-terminal SH3 domain. The DH domain is involved in RhoGTPase recognition and selectivity and stimulates the reorganization of the switch regions for GDP/GTP exchange []. The PH domain is implicated in directing membrane localization, allosteric regulation of guanine nucleotide exchange activity, and as a phospholipid-dependent regulator of GEF activity []. Vavs bind RhoGTPases including Rac1, RhoA, and RhoG, while other members of the GEF family are specific for a single RhoGTPase. This promiscuity is thought to be a result of its CRD [].PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner []. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity[]. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane []. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes [].
