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The authors use buthionine sulfoximine to mimic oxidative stress in T lymphocytes. Similar to what is seen in T cells from patients with RA [14], they find that LAT is displaced from the membrane under these conditions. They propose a model that, in an oxidizing environment, disulfide bonds form between cysteine residues in LAT, leading to a conformational change and subsequent membrane displacement.
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Gringhuis S.I., Papendrecht-van der Voort E.A., Leow A., Nivine Levarht E.W., Breedveld F.C., Verweij C.L. Effect of redox balance alterations on cellular localization of LAT and downstream T-cell receptor signaling pathways. Mol. Cell Biol. 22:2002;400-411 The authors use buthionine sulfoximine to mimic oxidative stress in T lymphocytes. Similar to what is seen in T cells from patients with RA [14], they find that LAT is displaced from the membrane under these conditions. They propose a model that, in an oxidizing environment, disulfide bonds form between cysteine residues in LAT, leading to a conformational change and subsequent membrane displacement.
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Yablonski D., Kadlecek T., Weiss A. Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain- binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT. Mol. Cell Biol. 21:2001;4208-4218.
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Lui S., Smith C., Arnold R., Kiefer F., McGlade C.J. The adaptor protein Gads (Grb2-related adaptor downstream of Shc) is implicated in coupling hemopoietic progenitor kinase-1 to the activated TCR. J. Immunol. 165:2000;1417-1426.
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Using a yeast two-hybrid screen, the authors identify the kinase HPK1 as a binding partner for the SLP-76 family member, CLNK. Even though they are believed to have different sets of binding partners, CLNK is able to rescue signaling in SLP-76 deficient Jurkat T cells, perhaps because of its associate with HPK1.
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Yu J., Riou C., Davidson D., Minhas R., Robson J.D., Julius M., Arnold R., Kiefer F., Veillette A. Synergistic regulation of immunoreceptor signaling by SLP-76-related adaptor Clnk and serine/threonine protein kinase HPK-1. Mol. Cell Biol. 21:2001;6102-6112 Using a yeast two-hybrid screen, the authors identify the kinase HPK1 as a binding partner for the SLP-76 family member, CLNK. Even though they are believed to have different sets of binding partners, CLNK is able to rescue signaling in SLP-76 deficient Jurkat T cells, perhaps because of its associate with HPK1.
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••], they find that mutation of these tyrosines leads to impaired BLNK binding, PLC-γ2 phosphorylation and calcium flux. These findings provide one explanation for BLNK membrane recruitment.
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••], they find that mutation of these tyrosines leads to impaired BLNK binding, PLC-γ2 phosphorylation and calcium flux. These findings provide one explanation for BLNK membrane recruitment.
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Siemasko, K.1
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0037321012
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••]. These papers support the notion that LAB partially functions like LAT in B cells.
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••]. These papers support the notion that LAB partially functions like LAT in B cells.
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The authors examine T-cell signaling in Grb2 heterozygous mice. Similar to the sensitivity of MAPKs to activation with PMA, they find that decreased levels of Grb2 affect the various MAPKs differently. In turn, these differences lead to decreased negative selection leaving positive selection intact. This paper effectively illustrates the consequences that gene dosage may have on physiologic processes.
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Gong Q., Cheng A.M., Akk A., Alberola-Ila J., Gong G., Pawson T., Chan A.C. Disruption of T cell signaling networks and development by Grb2 haploid insufficiency. Nat. Immunol. 2:2001;29-36 The authors examine T-cell signaling in Grb2 heterozygous mice. Similar to the sensitivity of MAPKs to activation with PMA, they find that decreased levels of Grb2 affect the various MAPKs differently. In turn, these differences lead to decreased negative selection leaving positive selection intact. This paper effectively illustrates the consequences that gene dosage may have on physiologic processes.
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Zhang L., Camerini V., Bender T.P., Ravichandran K.S. A nonredundant role for the adapter protein Shc in thymic T cell development. Nat. Immunol. 3:2002;749-755.
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Iwashima M., Takamatsu M., Yamagishi H., Hatanaka Y., Huang Y.Y., McGinty C., Yamasaki S., Koike T. Genetic evidence for Shc requirement in TCR-induced c-Rel nuclear translocation and IL-2 expression. Proc. Natl. Acad Sci. USA. 99:2002;4544-4549.
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Brdicka T., Pavlistova D., Leo A., Bruyns E., Korinek V., Angelisova P., Scherer J., Shevchenko A., Hilgert I., Cerny J.et al. Phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG), a novel ubiquitously expressed transmembrane adaptor protein, binds the protein tyrosine kinase csk and is involved in regulation of T cell activation. J. Exp. Med. 191:2000;1591-1604.
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Cutting edge: Fyn is essential for tyrosine phosphorylation of Csk- binding protein/phosphoprotein associated with glycolipid-enriched microdomains in lipid rafts in resting T cells
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The authors identify the Cbp binding protein EBP. They show that, when Cbp is overexpressed in cells, the reorganization of lipid rafts is impeded. This function appears to be dependent on the ability of Cbp to bind EBP. Therefore, they propose that the Cbp-EBP complex negatively regulates immune synapse formation.
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Itoh K., Sakakibara M., Yamasaki S., Takeuchi A., Arase H., Miyazaki M., Nakajima N., Okada M., Saito T. Cutting edge: negative regulation of immune synapse formation by anchoring lipid raft to cytoskeleton through Cbp-EBP50-ERM assembly. J. Immunol. 168:2002;541-544 The authors identify the Cbp binding protein EBP. They show that, when Cbp is overexpressed in cells, the reorganization of lipid rafts is impeded. This function appears to be dependent on the ability of Cbp to bind EBP. Therefore, they propose that the Cbp-EBP complex negatively regulates immune synapse formation.
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