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1.
J Immunol ; 212(6): 951-961, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38315039

RESUMO

Signal-transducing adaptor protein (STAP)-1 is an adaptor protein that is widely expressed in T cells. In this article, we show that STAP-1 upregulates TCR-mediated T cell activation and T cell-mediated airway inflammation. Using STAP-1 knockout mice and STAP-1-overexpressing Jurkat cells, we found that STAP-1 enhanced TCR signaling, resulting in increased calcium mobilization, NFAT activity, and IL-2 production. Upon TCR engagement, STAP-1 binding to ITK promoted formation of ITK-LCK and ITK-phospholipase Cγ1 complexes to induce downstream signaling. Consistent with the results, STAP-1 deficiency reduced the severity of symptoms in experimental autoimmune encephalomyelitis. Single-cell RNA-sequencing analysis revealed that STAP-1 is essential for accumulation of T cells and Ifng and Il17 expression in spinal cords after experimental autoimmune encephalomyelitis induction. Th1 and Th17 development was also attenuated in STAP-1 knockout naive T cells. Taken together, STAP-1 enhances TCR signaling and plays a role in T cell-mediated immune disorders.


Assuntos
Encefalomielite Autoimune Experimental , Camundongos , Animais , Transdução de Sinais , Ativação Linfocitária , Inflamação , Receptores de Antígenos de Linfócitos T , Proteínas Adaptadoras de Transdução de Sinal/genética
2.
Biochem Biophys Res Commun ; 488(1): 81-87, 2017 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-28478037

RESUMO

STAP-2 is an adaptor molecule regulating several signaling pathways, including TLRs and cytokine/chemokine receptors in immune cells. We previously reported that STAP-2 enhances SDF-1α-induced Vav1/Rac1-mediated T-cell chemotaxis. However, the detailed mechanisms of STAP-2 involvement in enhancing T-cell chemotaxis remain unknown. In the present study, we demonstrate that STAP-2 directly interacts with Pyk2, which is a key molecule in the regulation of SDF-1α/CXCR4-mediated T-cell chemotaxis, and increases phosphorylation of Pyk2. Pyk2 itself can induce STAP-2 Y250 phosphorylation, and this phosphorylation is critical for maximal interactions between STAP-2 and Pyk2. Finally, SDF-1α-induced T-cell chemotaxis is inhibited by treatment with Pyk2 siRNA or AG17, an inhibitor of Pyk2, in Jurkat cells overexpressing STAP-2. Taken together, the Pyk2/STAP-2 interaction is a novel mechanism to regulate SDF-1α-dependent T-cell chemotaxis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Quinase 2 de Adesão Focal/metabolismo , Fosfoproteínas/metabolismo , Linfócitos T/metabolismo , Humanos , Células Tumorais Cultivadas
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