title: SWAP-70-like adapter of T cells, an adapter protein that regulates early TCR-initiated signaling in Th2 lineage cells.
abstract: We describe the isolation of a protein, SWAP-70-like adapter of T cells (SLAT), which is expressed at high levels in thymocytes and differentiated Th2 cells. SLAT expression was upregulated in differentiating Th2 cells and downregulated in Th1 cells. Ectopic SLAT expression exerted positive or negative effects on IL-4 versus IFNgamma induction, respectively. TCR signaling induced translocation of SLAT to the immunological synapse and its association with ZAP-70 kinase. SLAT reduced the association of ZAP-70 with TCR-zeta and interfered with ZAP-70 but not Lck signaling. Consistent with these results, pharmacological inhibition of ZAP-70 also induced Th2 skewing. Thus, SLAT is a protein which plays a role in Th2 development and/or activation, perhaps by interfering with ZAP-70 signaling.
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Kun
authors.initials: K
authors.lastname: Bi
authors.forename: Rika
authors.initials: R
authors.lastname: Kitamura
authors.forename: Sooji
authors.initials: S
authors.lastname: Hong
authors.forename: Yoav
authors.initials: Y
authors.lastname: Altman
authors.forename: Akira
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tabata
authors.forename: Svetlana
authors.initials: S
authors.lastname: Lebedeva
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bushway
authors.forename: Amnon
authors.initials: A
authors.lastname: Altman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001693:Biological Transport, Active; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019672:Genes, T-Cell Receptor; D020662:Guanine Nucleotide Exchange Factors; D051379:Mice; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase
chemical_list: D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D020662:Guanine Nucleotide Exchange Factors; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases; D011948:Receptors, Antigen, T-Cell; D013267:Stilbenes; D051746:ZAP-70 Protein-Tyrosine Kinase; C473249:Def6 protein, mouse; C113365:Swap70 protein, mouse; C041525:3,3',4,5'-tetrahydroxystilbene; C497262:Zap70 protein, mouse