Vav2 Activates c-fos Serum Response Element and CD69 Expression but Negatively Regulates Nuclear Factor of Activated T Cells and Interleukin-2 Gene Activation in T Lymphocyte

Tartare‐Deckert, Sophie; Monthouel, Marie-Noëlle; Charvet, Céline; Foucault, Isabelle; Obberghen, Emmanuel Van; Bernard, Alain; Deckert, Marcel

doi:10.1074/jbc.m010588200

Cited by 26 publications

(26 citation statements)

References 53 publications

(79 reference statements)

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“…The cDNA encoding Myc-tagged Vav1 and VSV-tagged ezrin were previously described. 33,34 A20.2J cell transfection. A20.2J (A20) mouse B cells expressing short hairpin (sh) SHP-1 siRNA or control siRNA were established by transfecting cells at 300 V for 20 ms with 20 mg of mouse SHP-1 shRNAi (shRNAi SHP-1) or control shRNAi (shRNAi control) using the Amaxa Nucleofection Technologyt (Amaxa, Cologne, Germany) and stable cells were selected with geneticin.…”

Section: Discussionmentioning

confidence: 99%

Regulating Vav1 phosphorylation by the SHP-1 tyrosine phosphatase is a fine-tuning mechanism for the negative regulation of DISC formation and Fas-mediated cell death signaling

et al. 2007

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The actin cytoskeleton association is required for caspase 8-independent Fas/CD95 receptor internalization, a critical step for an optimal death-inducing signaling complex formation along the endocytic pathway, leading to efficient activation of the caspase cascade and, ultimately, cell death. However, the way in which this initiation phase of Fas receptor signaling is regulated is still unknown. We report herein that, in B cells, upon Fas engagement, the tyrosine phosphatase SHP-1-regulated Vav dephosphorylation, by downmodulating the Fas-ezrin-actin linkage is a fine-tune switch-off mechanism that the cell uses as a way to terminate the receptor internalization, controlling therefore the time and extent of the DISC formation and cell death.

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Section: Discussionmentioning

confidence: 99%

Regulating Vav1 phosphorylation by the SHP-1 tyrosine phosphatase is a fine-tuning mechanism for the negative regulation of DISC formation and Fas-mediated cell death signaling

et al. 2007

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“…The interaction of Vav with active Syk leads to Vav phosphorylation on tyrosine and the activation of its GEF activity (13,43,50,53,59,69,74,75). We examined how the different linker B phosphotyrosines influence this interaction by taking advantage of the availability of DT40 B cells engineered to lack endogenous Syk (73).…”

Section: Effect Of Syk Y342 and Y346 Phosphorylation On Recognition Bmentioning

confidence: 99%

“…Syk associates with Vav family proteins and phosphorylates them on tyrosines that regulate their activity (13,43,50,53,59,69,74,75). This physical association occurs between the Vav SH2 domain and the Syk linker B region, which separates the tandem SH2 domains from the catalytic domain and contains phosphotyrosines 342 and 346 (based on the numbering system for murine Syk).…”

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confidence: 99%

“…Vav proteins enhance many signaling pathways mediated by Syk-associated receptors, including the activation of phospholipase C-␥ (PLC-␥) and the mobilization of intracellular calcium, the activation of phosphoinositide 3-kinase (PI3K) and Akt, the activation of the Ras/Erk pathway, the promotion of cytoskeletal rearrangements, and the inside-out activation of integrins. While Vav proteins serve as GEFs for Rac/Rho family GTPases, they also act as scaffolds, a function that promotes the assembly of signaling complexes but does not require GEF activity (66).Syk associates with Vav family proteins and phosphorylates them on tyrosines that regulate their activity (13,43,50,53,59,69,74,75). This physical association occurs between the Vav SH2 domain and the Syk linker B region, which separates the tandem SH2 domains from the catalytic domain and contains phosphotyrosines 342 and 346 (based on the numbering system for murine Syk).…”

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confidence: 99%

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Two Closely Spaced Tyrosines Regulate NFAT Signaling in B Cells via Syk Association with Vav

Chen

Martin

Gorenstein

et al. 2011

Molecular and Cellular Biology

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Syk is a cytoplasmic protein tyrosine kinase that regulates cellular responses mediated by a variety of membrane receptors with intracellular signaling modules known as immunoreceptor tyrosine-based activation motifs (ITAMs) (23, 52). Examples of ITAM/Syk receptors include the B and T cell receptors for antigen, the immunoglobulin receptors FcεRI, Fc␥RI, and Fc␥RIIa, the activating NK cell receptors, and integrins. When these receptors are engaged, a pair of tyrosines within the ITAM become phosphorylated to create a docking site for Syk's N-terminal pair of SH2 domains. Syk binding to the ITAM leads to Syk activation and phosphorylation on several tyrosines to generate sites that participate in protein-protein interactions. Thus, activated Syk at the site of the clustered receptor participates in the formation of a signaling complex. This "signalosome" contains multiple effector proteins that include members of the Vav family of guanine nucleotide exchange factors (GEFs) (13,14).Among the three members of the Vav family, Vav1 is restricted largely to hematopoietic cells while Vav2 and Vav3 are more widely distributed (8,55,67,77). Vav proteins have both unique and redundant functions in the immune system, as a loss of Vav1 produces severe defects in T cell development and signaling, while the loss of more than one Vav family member is needed to produce similar defects in B cells (12,17,21,75,76). Vav proteins enhance many signaling pathways mediated by Syk-associated receptors, including the activation of phospholipase C-␥ (PLC-␥) and the mobilization of intracellular calcium, the activation of phosphoinositide 3-kinase (PI3K) and Akt, the activation of the Ras/Erk pathway, the promotion of cytoskeletal rearrangements, and the inside-out activation of integrins. While Vav proteins serve as GEFs for Rac/Rho family GTPases, they also act as scaffolds, a function that promotes the assembly of signaling complexes but does not require GEF activity (66).Syk associates with Vav family proteins and phosphorylates them on tyrosines that regulate their activity (13,43,50,53,59,69,74,75). This physical association occurs between the Vav SH2 domain and the Syk linker B region, which separates the tandem SH2 domains from the catalytic domain and contains phosphotyrosines 342 and 346 (based on the numbering system for murine Syk). Syk linker B interacts with multiple binding partners depending on which tyrosines in linker B are phosphorylated and the stoichiometry of this phosphorylation (23). As such, Syk linker B harbors the unusual site of two closely space tyrosines, which are recognized by a single SH2 domain of particular Syk binding partners. These interactions influence the ability of the kinase to couple ITAM-bearing receptors to the many different intracellular signaling pathways that are regulated following receptor engagement (23,52).Vav1 SH2 adopts the typical fold of an SH2 domain, including a central ␤-sheet flanked by two ␣-helices (Protein Data Bank [PDB] designation: 2CRH). The nonaromatic hydrophobic Ile r...

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“…Vav protein contains 11 potential tyrosine phosphorylation sites and also putative serine/threonine phosphorylation sites (38). Several tyrosine kinases have been involved in Vav activation including the Src (Lck, Fyn) and Syk families (ZAP-70, Syk) (39). It is possible that Cybr could interact with one or more of these kinases as it has been shown for Tamalin, thereby facilitating Vav phosphorylation (34).…”

Section: Discussionmentioning

confidence: 99%

Cytohesin Binder and Regulator Augments T Cell Receptor-induced Nuclear Factor of Activated T Cells·AP-1 Activation through Regulation of the JNK Pathway

Chen

Coffey

Bourgoin

et al. 2006

Journal of Biological Chemistry

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Vav2 Activates c-fos Serum Response Element and CD69 Expression but Negatively Regulates Nuclear Factor of Activated T Cells and Interleukin-2 Gene Activation in T Lymphocyte

Cited by 26 publications

References 53 publications

Regulating Vav1 phosphorylation by the SHP-1 tyrosine phosphatase is a fine-tuning mechanism for the negative regulation of DISC formation and Fas-mediated cell death signaling

Regulating Vav1 phosphorylation by the SHP-1 tyrosine phosphatase is a fine-tuning mechanism for the negative regulation of DISC formation and Fas-mediated cell death signaling

Two Closely Spaced Tyrosines Regulate NFAT Signaling in B Cells via Syk Association with Vav

Cytohesin Binder and Regulator Augments T Cell Receptor-induced Nuclear Factor of Activated T Cells·AP-1 Activation through Regulation of the JNK Pathway

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