Requirement for Tec kinases Rlk and ltk in T cell receptor signaling and immunity

Edward M. Schaeffer, Jayanta Debnath, George Yap, Daniel McVicar, X. Charlene Liao, Dan R. Littman, Alan Sher, Harold E. Varmus, Michael J. Lenardo, Pamela L. Schwartzberg

Research output: Contribution to journalArticlepeer-review

312 Scopus citations

Abstract

T cell receptor (TCR) signaling requires activation of Zap-70 and Src family tyrosine kinases, but requirements for other tyrosine kinases are less clear. Combined deletion in mice of two Tec kinases, Rlk and ltk, caused marked defects in TCR responses including proliferation, cytokine production, and apoptosis in vitro and adaptive immune responses to Toxoplasma gondii in vivo. Molecular events immediately downstream from the TCR were intact in rlk(-/-)itk(-I-) cells, but intermediate events including inositol trisphosphate production, calcium mobilization, and mitogen-activated protein kinase activation were impaired, establishing Tec kinases as critical regulators of TCR signaling required for phospholipase C-γ activation.

Original languageEnglish (US)
Pages (from-to)638-641
Number of pages4
JournalScience
Volume284
Issue number5414
DOIs
StatePublished - Apr 23 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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