The Role of Tec Protein-tyrosine Kinase in T Cell Signaling

Yang, Wu-Chang; Ghiotto, Marguerite; Barbarat, Bernadette; Olive, Daniel

doi:10.1074/jbc.274.2.607

Cited by 96 publications

(109 citation statements)

References 65 publications

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“…First, Dok1 is a major p-Y protein downstream of v-Abl, v-Src, v-Fps, v-Fms, p210 bcr-abl , and epidermal growth factor, platelet-derived growth factor, colony-stimulating factor, insulin, insulin-like growth factor, vascular endothelial growth factor, antigen, Fc␥, or CD28 receptor signaling pathways (13,(34)(35)(36)(37)(38)(39). Dok1 is an abundant tyrosine phosphorylated protein in pervanadate-treated B lymphoma cells, and p-Y Dok1 is an abundant p-Y protein that binds in vitro to SH2D1A.…”

Section: Discussionmentioning

confidence: 99%

The X-linked lymphoproliferative syndrome gene product SH2D1A associates with p62^dok(Dok1) and activates NF-κB

Sylla

Murphy

Cahir-McFarland³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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The X-linked lymphoproliferative syndrome (XLP) is a genetic disorder in which affected males have a morbid or fatal response to Epstein-Barr virus infection. The XLP deficiency has been mapped to a gene encoding a 128-residue protein, SH2D1A, which is comprised principally of a Src homology 2 (SH2) domain. We now report that SH2D1A associates with Dok1, a protein that interacts with Ras-GAP, Csk, and Nck. An SH2D1A SH2 domain mutant that has been identified in XLP does not associate with Dok1, in accord with the hypothesis that this interaction is linked to XLP. The association of SH2D1A with Dok1 also depends on phosphorylation of Dok1 Y 449 in the sequence ALYSQVQK. Further, overexpression of SH2D1A is found to activate NF-B in 293T cells. NF-B activation by SH2D1A does not depend on the wild-type SH2 domain and is inhibited by a dominant-negative I B kinase ␤. Thus, SH2D1A can affect multiple intracellular signaling pathways that are potentially important in the normal effective host response to Epstein-Barr virus infection. Epstein-Barr virus ͉ genetic disease

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Section: Discussionmentioning

confidence: 99%

The X-linked lymphoproliferative syndrome gene product SH2D1A associates with p62^dok(Dok1) and activates NF-κB

Sylla

Murphy

Cahir-McFarland³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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“…These adapters can be phosphorylated by an antigen-independent signal involving costimulatory molecules such as CD2 or CD28. [17][18][19][20] Cloning of three members (Dok1, Dok2 and Dok3) raises the possibility to perform database searches to identify new putative Dok protein members. A first screening has been performed with a sequence containing a high homology between Dok-1, Dok-2 and also Dok-3.…”

Section: Introductionmentioning

confidence: 99%

DOK4 and DOK5: new dok-related genes expressed in human T cells

et al. 2003

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Dok proteins are adapter proteins involved in signal transduction. Several intracellular proteins expressed in lymphocytes meet the criteria of membrane-associated adapter proteins such as members of the Dok family. To understand the role and the formation of multiprotein networks involving Dok proteins in T lymphocytes, we search for potential additional members of this family. Here, we describe the two new human dok-related genes DOK4 and DOK5 and present data showing the expression of DOK4 and DOK5 genes in T cells. These genes are the orthologues of mouse Dok4 and Dok5 genes. Based on analysis of phylogenetic trees and exon/intron structure of Dok family members, DOK4 and DOK5 define a subfamily within dok genes distinct from DOK1, DOK2 and DOK3. So, Dok-4 and Dok-5 molecules constitute a new group of adapter proteins in T cells, requiring further functional analysis.

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“…Two of them, Itk and Txk, are predominantly expressed in T cells, whereas Tec is more broadly distributed among all hemopoietic cell types, including T cells (11)(12)(13). Despite many biochemical studies linking Tec kinases with numerous cell surface receptors (14), the precise role(s) of Tec kinases in T cell signal transduction are not well understood.…”

Section: S Timulation Of the Tcr On Mature T Cells Induces A Seriesmentioning

confidence: 99%

“…Although Tec has been implicated in cytokine receptor signaling in nonlymphoid cells (21), little is known about the role of Tec in T cells. The data that has been generated, implicating Tec in both TCR and CD28 signaling, has predominantly relied on transient transfections and overexpression systems (13,22).…”

Section: S Timulation Of the Tcr On Mature T Cells Induces A Seriesmentioning

confidence: 99%

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Tec Kinase Signaling in T Cells Is Regulated by Phosphatidylinositol 3-Kinase and the Tec Pleckstrin Homology Domain

Yang

Ching

Tsoukas

et al. 2001

The Journal of Immunology

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Tec, the prototypical member of the Tec family of tyrosine kinases, is abundantly expressed in T cells and other hemopoietic cell types. Although the functions of Itk and Txk have recently been investigated, little is known about the role of Tec in T cells. Using antisense oligonucleotide treatment to deplete Tec protein from primary T cells, we demonstrate that Tec plays a role in TCR signaling leading to IL-2 gene induction. Interestingly, Tec kinases are the only known family of tyrosine kinases containing a pleckstrin homology (PH) domain. Using several PH domain mutants overexpressed in Jurkat T cells, we show that the Tec PH domain is required for Tec-mediated IL-2 gene induction and TCR-mediated Tec tyrosine phosphorylation. Furthermore, we show that Tec colocalizes with the TCR after TCR cross-linking, and that both the Tec PH and Src homology (SH) 2 domains play a role in this association. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, abolishes Tec-mediated IL-2 gene induction and Tec tyrosine phosphorylation, and partially suppresses Tec colocalization with the activated TCR. Thus, our data implicate the Tec kinase PH domain and phosphatidylinositol 3-kinase in Tec signaling downstream of the TCR.

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The Role of Tec Protein-tyrosine Kinase in T Cell Signaling

Cited by 96 publications

References 65 publications

The X-linked lymphoproliferative syndrome gene product SH2D1A associates with p62^dok(Dok1) and activates NF-κB

The X-linked lymphoproliferative syndrome gene product SH2D1A associates with p62^dok(Dok1) and activates NF-κB

DOK4 and DOK5: new dok-related genes expressed in human T cells

Tec Kinase Signaling in T Cells Is Regulated by Phosphatidylinositol 3-Kinase and the Tec Pleckstrin Homology Domain

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The Role of Tec Protein-tyrosine Kinase in T Cell Signaling

Cited by 96 publications

References 65 publications

The X-linked lymphoproliferative syndrome gene product SH2D1A associates with p62dok(Dok1) and activates NF-κB

The X-linked lymphoproliferative syndrome gene product SH2D1A associates with p62dok(Dok1) and activates NF-κB

DOK4 and DOK5: new dok-related genes expressed in human T cells

Tec Kinase Signaling in T Cells Is Regulated by Phosphatidylinositol 3-Kinase and the Tec Pleckstrin Homology Domain

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Resources

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The X-linked lymphoproliferative syndrome gene product SH2D1A associates with p62^dok(Dok1) and activates NF-κB

The X-linked lymphoproliferative syndrome gene product SH2D1A associates with p62^dok(Dok1) and activates NF-κB