Intensity and duration of TCR signaling is limited by p38 phosphorylation of ZAP-70T293 and destabilization of the signalosome

• Verfasst von: Torchia, Maria Letizia Giardino [VerfasserIn]
• Verfasst von: Gaida, Matthias [VerfasserIn]
• Titel: Intensity and duration of TCR signaling is limited by p38 phosphorylation of ZAP-70T293 and destabilization of the signalosome
• Verf.angabe: Maria Letizia Giardino Torchia, Debjani Dutta, Paul R. Mittelstadt, June Guha, Matthias M. Gaida, Kamonwan Fish, Valarie A. Barr, Itoro O. Akpan, Lawrence E. Samelson, Harichandra D. Tagad, Subrata Debnath, Lisa M. Miller Jenkins, Ettore Appella, and Jonathan D. Ashwell
• E-Jahr: 2018
• Jahr: February 12, 2018
• Umfang: 6 S.
• Fussnoten: Im Titel T293 hochgestellt ; Gesehen am 12.08.2019
• Titel Quelle: Enthalten in: National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America
• Ort Quelle: Washington, DC : National Acad. of Sciences, 1915
• Jahr Quelle: 2018
• Band/Heft Quelle: 115(2018), 9, Seite 2174-2179
• ISSN Quelle: 1091-6490
• DOI: doi:10.1073/pnas.1713301115
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: immune synapse
• Sach-SW: MAP kinase
• Sach-SW: signal transduction
• Sach-SW: T cell antigen receptor
• K10plus-PPN: 1671165233

Abstract

ZAP-70 is a tyrosine kinase that is essential for initiation of T cell antigen receptor (TCR) signaling. We have found that T cell p38 MAP kinase (MAPK), which is directly phosphorylated and activated by ZAP-70 downstream of the TCR, in turn phosphorylates Thr-293 in the interdomain B region of ZAP-70. Mutant T cells expressing ZAP-70 with an alanine substitution at this residue (ZAP-70T293A) had enhanced TCR proximal signaling and increased effector responses. Lack of ZAP-70T293 phosphorylation increased association of ZAP-70 with the TCR and prolonged the existence of TCR signaling microclusters. These results identify a tight negative feedback loop in which ZAP-70-activated p38 reciprocally phosphorylates ZAP-70 and destabilizes the signaling complex.