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Nat Immunol. 2005 Apr;6(4):390-5. Epub 2005 Feb 27.

Alternative p38 activation pathway mediated by T cell receptor-proximal tyrosine kinases.

Author information

1
Gene Response Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Abstract

Signaling-responsive MAP kinases (MAPKs) are key in mediating immune responses and are activated through the phosphorylation of a Thr-X-Tyr motif by upstream MAPK kinases. Here we show that T cells stimulated through the T cell receptor (TCR) used an alternative mechanism in which p38 was phosphorylated on Tyr323 and subsequently autophosphorylated residues Thr180 and Tyr182. This required the TCR-proximal tyrosine kinase Zap70 but not the adaptor protein LAT, which was required for activation of extracellular signal-regulated protein kinase MAPKs. TCR activation of p38 lacking Tyr323 was diminished, and blocking of p38 activity prevented p38 dual phosphorylation in normal T cells but not in B cells. Thus, phosphorylation of Tyr323 dependent on the tyrosine kinase Lck and mediated by Zap70 serves as an important mechanism for TCR activation of p38 in T cells.

PMID:
15735648
DOI:
10.1038/ni1177
[Indexed for MEDLINE]

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