Signal Transduction by CD28 Costimulatory Receptor on T Cells

Nunès, Jacques A.; Truneh, Alemseged; Olive, Daniel; Cantrell, Doreen A.

doi:10.1074/jbc.271.3.1591

Cited by 78 publications

(51 citation statements)

References 54 publications

(53 reference statements)

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“…COS-7 cells were maintained in Dulbecco's modified Eagle's medium supplemented with 10% fetal calf serum, penicillin, streptomycin, and glutamate. Besides human Jurkat T leukemia cells JH6.2 (38), murine fibroblast cell line 3T6, murine IL-3-dependent pro-B cell line BAF3, human monocytic cell line THP1, human myeloid cell line KG1a, human pre-B cell line Nalm6, and human myeloma cell line U266 were grown in RPMI 1640 medium supplemented with 10% fetal calf serum, penicillin, streptomycin, and glutamate except BAF3 medium which was further supplemented with IL-3.…”

Section: Methodsmentioning

confidence: 99%

“…p62 dok but Not CD28 Is an in Vivo Substrate for Tec-TCR activation results in tyrosine phosphorylation of substrates such as Cbl (p120), SLP76 (p76), and p36/38 (LAT) (50 -52). CD28 activation also leads to tyrosine phosphorylation of substrates such as p95 vav , an adaptor molecule p62, Cbl, the catalytic subunit of PI 3-kinase (p110), and CD28 itself (32)(33)(34)(35)46). To understand the role of Tec kinase in TCR and CD28 pathways, we tried to find its substrate(s).…”

Section: Tec Expression In Myeloid and Lymphoid Cells Including Tmentioning

confidence: 99%

“…To understand the role of Tec kinase in TCR and CD28 pathways, we tried to find its substrate(s). Molecule(s) of 62 kDa associated to Ras GAP was demonstrated to be phosphorylated upon CD28 but not CD3 stimulation (35). One molecule associated to Ras GAP has been recently cloned and called p62 dok (53,54).…”

Section: Tec Expression In Myeloid and Lymphoid Cells Including Tmentioning

confidence: 99%

“…p62 dok containing some functional domains (PH, PTB, and tyrosine residues) is a downstream substrate of kinases such as Lck, Src, or Abl. Stimulation of CD2 and CD28 but not CD3 can induce tyrosine phosphorylation of the p62 ras GAPassociated protein (35,71). We first indicated that p62 dok is an in vivo substrate for Tec kinase but not Itk in COS-7 cells.…”

mentioning

confidence: 99%

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

Yang¹,

Ghiotto

Barbarat

et al. 1999

Journal of Biological Chemistry

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103

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Section: Methodsmentioning

confidence: 99%

Section: Tec Expression In Myeloid and Lymphoid Cells Including Tmentioning

confidence: 99%

Section: Tec Expression In Myeloid and Lymphoid Cells Including Tmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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

Yang¹,

Ghiotto

Barbarat

et al. 1999

Journal of Biological Chemistry

Self Cite

103

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“…In TCR-stimulated cells, there is a rapid formation of a complex between Sos/Grb2 and a 36-kDa membrane protein, LAT, that is a substrate for the TCR-induced tyrosine kinases (38 -40). Antibody-mediated aggregation of CD28 can also activate Ras (41). Grb2 has been shown to bind to CD28 following ligation of CD28 (28,29).…”

Section: Engagement Of the T Cell Receptor (Tcr)mentioning

confidence: 99%

Grb2 Forms an Inducible Protein Complex with CD28 through a Src Homology 3 Domain-Proline Interaction

Okkenhaug

Rottapel

1998

Journal of Biological Chemistry

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CD28 provides a costimulatory signal that results in optimal activation of T cells. The signal transduction pathways necessary for CD28-mediated costimulation are presently unknown. Engagement of CD28 leads to its tyrosine phosphorylation and subsequent binding to Src homology 2 (SH2)-containing proteins including the p85 subunit of phosphatidylinositol 3-kinase (PI3K); however, the contribution of PI3K to CD28-dependent costimulation remains controversial. Here we show that CD28 is capable of binding the Src homology 3 (SH3) domains of several proteins, including Grb2. The interaction between Grb2 and CD28 is mediated by the binding of Grb2-SH3 domains to the C-terminal diproline motif present in the cytoplasmic domain of CD28. While the affinity of the C-terminal SH3 domain of Grb2 for CD28 is greater than that of the N-terminal SH3 domain, optimal binding requires both SH3 domains. Ligation of CD28, but not tyrosine-phosphorylation, is required for the SH3-mediated binding of Grb2 to CD28. We propose a model whereby the association of Grb2 with CD28 occurs via an inducible SH3-mediated interaction and leads to the recruitment of tyrosine-phosphorylated proteins such as p52 shc bound to the SH2 domain of Grb2. The inducible interaction of Grb2 to the C-terminal region of CD28 may form the basis for PI3K-independent signaling through CD28. Engagement of the T cell receptor (TCR)1 by the major histocompatibility complex-peptide complex in the absence of costimulatory molecules is insufficient to induce production of cytokines and can render the T cells unresponsive to further antigenic challenge (1). CD28 is preeminent among a group of receptors, including 4 -1BB and CD43, that can provide costimulatory signals to T cells (2-4). CD28 is a type 1 transmembrane protein of the Ig superfamily, which is expressed on the cell surface as a glycosylated homodimer (5). CD28 costimulation of TCR-dependent responses increases IL-2 production (6, 7), prevents the induction of anergy (8), and renders T cells resistant to apoptotic cell death (9 -11). These effects are mediated by increased transcription of cytokine genes through the activation of a composite NF-B and AP-1 transcriptional element (12, 13), the stabilization of cytokine mRNAs (14), and the expression of the survival protein, Bclx L (9). TCR-mediated T cell activation is sensitive to the immunosuppressive drug cyclosporin, while those pathways activated by CD28 are not, suggesting that costimulatory pathways are distinct from those activated by the TCR (7). Early biochemical events induced through CD28 include tyrosine phosphorylation (15, 16) and activation of PI3K (17-19) and acidic sphingomyelinase (20). The identity of the signal transduction pathways that are required for CD28-mediated costimulation are presently unknown.The cytoplasmic domain of CD28 contains no recognized intrinsic enzymatic activity; however, CD28 has been reported to associate with signaling proteins following ligation. Phosphorylation of CD28 on tyrosine 173 within the motif YMNM pres...

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CD28 affects the earliest signaling events generated by TCR engagement

Tuosto

Acuto

1998

Eur. J. Immunol.

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The efficiency and magnitude of T cell responses are influenced by ligation of the co-stimulatory receptor CD28 by B7 molecules expressed on antigen-presenting cells (APC). In contrast to most previous studies in which agonistic anti-TCR/CD3 and anti-CD28 antibod-ies were employed, here we have investigated the contribution of CD28 to T cell activation under physiological conditions of antigen presentation. Jurkat T cells and primary T cells from TCR-transgenic mice stimulated with superantigen and antigen, respectively, presented by B7-expressing APC were utilized. In both systems we show that inhibiting CD28/ B7 interaction resulted in impaired TCR-induced tyrosine phosphorylation of the signal-transducing´chaintransducing´transducing´chain and ZAP-70. Consistent with a blockade of TCR-proximal signaling events, Jurkat cells stimulated in the absence of CD28 ligation were found to have strongly diminished tyrosine phosphorylation of cellular substrates and downstream signaling pathways such as Ca 2+ /calcineurin, ERK/MAPK and JNK. Our results provide evidence for a role of CD28 in enhancing TCR signaling capacity during the earliest stages of T cell : APC interaction .

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Signal Transduction by CD28 Costimulatory Receptor on T Cells

Cited by 78 publications

References 54 publications

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

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

Grb2 Forms an Inducible Protein Complex with CD28 through a Src Homology 3 Domain-Proline Interaction

CD28 affects the earliest signaling events generated by TCR engagement

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