cd20867

protein kinase C conserved region 1 (C1 domain) found in VAV1 protein

CDD entry
Member databaseCDD
CDD typedomain
Short nameC1_VAV1
SetC1

Description

VAV1 is expressed predominantly in the hematopoietic system and 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. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.
[13, 18, 8, 2, 10, 6, 14, 16, 7, 15, 12, 19, 11, 5, 9, 17, 3, 1, 4]

References

1.VAV's got rhythm. Baylis HA. Cell 123, 5-7, (2005). PMID: 16213207

2.Vav1: an oncogene that regulates specific transcriptional activation of T cells. Katzav S. Blood 103, 2443-51, (2004). View articlePMID: 14592821

3.Structure and function of vav. Romero F, Fischer S. Cell. Signal. 8, 545-53, (1996). View articlePMID: 9115846

4.The role of Vav proteins in B cell responses. Turner M. Adv. Exp. Med. Biol. 512, 29-34, (2002). PMID: 12405184

5.Recognition and activation of Rho GTPases by Vav1 and Vav2 guanine nucleotide exchange factors. Heo J, Thapar R, Campbell SL. Biochemistry 44, 6573-85, (2005). View articlePMID: 15850391

6.CD28 costimulation: a source of Vav-1 for TCR signaling with the help of SLP-76? Michel F, Acuto O. Sci. STKE 2002, pe35, (2002). View articlePMID: 12165654

7.An active form of Vav1 induces migration of mammary epithelial cells by stimulating secretion of an epidermal growth factor receptor ligand. Wilsbacher JL, Moores SL, Brugge JS. Cell Commun Signal 4, 5, (2006). PMID: 16709244

8.VAV1: a new target in pancreatic cancer? Denicola G, Tuveson DA. Cancer Biol Ther 4, 509-11, (2005). PMID: 15970675

9.Vav-family proteins in T-cell signalling. Tybulewicz VL. Curr. Opin. Immunol. 17, 267-74, (2005). View articlePMID: 15886116

10.Vav1: a key signal transducer downstream of the TCR. Tybulewicz VL, Ardouin L, Prisco A, Reynolds LF. Immunol. Rev. 192, 42-52, (2003). View articlePMID: 12670394

11.Acidic region tyrosines provide access points for allosteric activation of the autoinhibited Vav1 Dbl homology domain. Amarasinghe GK, Rosen MK. Biochemistry 44, 15257-68, (2005). View articlePMID: 16285729

12.Structural basis of guanine nucleotide exchange mediated by the T-cell essential Vav1. Chrencik JE, Brooun A, Zhang H, Mathews II, Hura GL, Foster SA, Perry JJ, Streiff M, Ramage P, Widmer H, Bokoch GM, Tainer JA, Weckbecker G, Kuhn P. J. Mol. Biol. 380, 828-43, (2008). View articlePMID: 18589439

13.Vav1: a hematopoietic signal transduction molecule involved in human malignancies. Katzav S. Int. J. Biochem. Cell Biol. 41, 1245-8, (2009). View articlePMID: 19100858

14.Tyrosine residues at the carboxyl terminus of Vav1 play an important role in regulation of its biological activity. Lazer G, Pe'er L, Farago M, Machida K, Mayer BJ, Katzav S. J Biol Chem 285, 23075-85, (2010). PMID: 20457609

15.Structural and energetic mechanisms of cooperative autoinhibition and activation of Vav1. Yu B, Martins IR, Li P, Amarasinghe GK, Umetani J, Fernandez-Zapico ME, Billadeau DD, Machius M, Tomchick DR, Rosen MK. Cell 140, 246-56, (2010). View articlePMID: 20141838

16.The association of Sam68 with Vav1 contributes to tumorigenesis. Lazer G, Pe'er L, Schapira V, Richard S, Katzav S. Cell. Signal. 19, 2479-86, (2007). View articlePMID: 17855053

17.Vav proteins, masters of the world of cytoskeleton organization. Hornstein I, Alcover A, Katzav S. Cell. Signal. 16, 1-11, (2004). View articlePMID: 14607270

18.Flesh and blood: the story of Vav1, a gene that signals in hematopoietic cells but can be transforming in human malignancies. Katzav S. Cancer Lett. 255, 241-54, (2007). View articlePMID: 17590270

19.Crucial structural role for the PH and C1 domains of the Vav1 exchange factor. Rapley J, Tybulewicz VL, Rittinger K. EMBO Rep. 9, 655-61, (2008). View articlePMID: 18511940

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