Article

Signaling via the T cell antigen receptor induces phosphorylation of Stat1 on serine 727

Department of Immunology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Journal of Biological Chemistry (Impact Factor: 4.6). 07/2000; 275(22):16574-8. DOI: 10.1074/jbc.M910149199
Source: PubMed

ABSTRACT The Stat1 transcription factor plays a pivotal role in both, the antiviral and antigrowth actions of interferons. Stat1 acquires the ability to bind DNA by becoming phosphorylated on Tyr(701). However, to effectively stimulate gene transcription, it must also be phosphorylated on Ser(727). We show that engagement of T cell antigen receptor (TCR)/CD3 complex in either Jurkat cells or peripheral blood lymphocytes stimulates phosphorylation of Ser(727) but not Tyr(701) of Stat1. This process does not require the expression of tyrosine kinases Lck and Zap-70. Interestingly, pretreatment of T cells with the Src kinase inhibitor PP1 completely abrogated CD3-mediated serine phosphorylation of Stat1, whereas inhibitors to MEK1 and phosphatidylinositol 3-kinase had no effect. Phosphorylation of Ser(727) of Stat1 in T cells is not restricted to TCR/CD3 but also results when cells are stimulated via the costimulatory molecule CD28. The combination of CD3 and CD28 did not augment phosphorylation of Stat1 Ser(727). Surprisingly, Stat1-mediated transcriptional activity in response to IFN-alpha was enhanced with CD3 stimulation, whereas CD3 alone had little effect. These findings suggest that Stat1 is a signaling molecule in TCR signaling and may play a role in T cell function.

0 Followers
 · 
50 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Diverse cellular responses to external cues are controlled by a small number of signal-transduction pathways, but how the specificity of functional outcomes is achieved remains unclear. Here we describe a mechanism for signal integration based on the functional coupling of two distinct signaling pathways widely used in leukocytes: the ITAM pathway and the Jak-STAT pathway. Through the use of the receptor for interferon-γ (IFN-γR) and the ITAM adaptor Fcγ as an example, we found that IFN-γ modified responses of the phagocytic antibody receptor FcγRI (CD64) to specify cell-autonomous antimicrobial functions. Unexpectedly, we also found that in peritoneal macrophages, IFN-γR itself required tonic signaling from Fcγ through the kinase PI(3)K for the induction of a subset of IFN-γ-specific antimicrobial functions. Our findings may be generalizable to other ITAM and Jak-STAT signaling pathways and may help explain signal integration by those pathways.
    Nature Immunology 03/2014; DOI:10.1038/ni.2845 · 24.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multinuclear MAS NMR together with XRD and N2 adsorption were employed to characterize the local structures of heterogeneous Ph3P-Rh/SBA-15 and supported homogeneous HRh (CO) (PPh3)3/SBA-15 catalysts. It is found that Ph3P-Rh complex can be tightly grafted on SBA-15 through the Si-O-Rh bonds while much less such bonds are formed in the supported homogeneous counterpart. This can be correlated to the longer catalytic life of heterogeneous PPh3-Rh/SBA-15 for propylene hydroformylation.
  • [Show abstract] [Hide abstract]
    ABSTRACT: CD4(+)CD25(high)Foxp3(+) regulatory T cells (Tregs), as an active mechanism of immune suppression, have been targeted due to their tremendous therapeutic potentials to prevent autoimmune diseases, transplant rejection, and to inhibit progression of tumors and chronic viral diseases. In last twelve years, substantial molecular differences between homeostasis of Tregs and that of other subsets of T cells and some factors specific in regulation of Treg survival have been characterized. In this overview we focus on panoramic reviewing of 91 factors, pathways and drugs, both well-characterized and newly defined, regarding the survival and homeostasis of Tregs in the following sections: 2: Tregs, an essential mechanism of immune tolerance; 3: nTregs, aTregs and other regulatory T cells; 4: co-stimulation receptor signaling; 5: innate immunity and Toll-like receptor (TLR) signaling; 6: effects of cytokines and hormones; 7: transcription factors in regulation of Tregs; 8: Treg intracellular signaling and IL-4 cytokines exert their protective function on CD4+ T cells in the presence of soluble CD4 ligands, shows that they are able to reduce susceptibility to Bax-mediated apoptosis but not to CD95-dependent apoptotic pathways (289). A recent report from our laboratory showed that Tregs express higher levels of Bax than CD4+CD25- T cells (278). Our results further demonstrated for the first time that removal of Tregs via a Bax-dependent apoptosis pathway significantly enhances anti-self-tumor antigen immune responses (278), which points out that apoptosis pathway of Tregs is a new therapeutic target for treatment of immune related diseases.
    Frontiers in Bioscience 01/2008; 13(13). DOI:10.2741/2775 · 4.25 Impact Factor