Requirement for Tec Kinases Rlk and Itk in T Cell Receptor Signaling and Immunity

Science  23 Apr 1999:
Vol. 284, Issue 5414, pp. 638-641
DOI: 10.1126/science.284.5414.638

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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 Itk, 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 inrlk −/− itk −/− 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.

  • * These authors contributed equally to this work.

  • Present address: Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.

  • To whom correspondence should be addressed. E-mail: pams{at}

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