Biochemical and genetic analyses of the Tec kinases Itk and Rlk/Txk

M. J. Czar, J. Debnath, E. M. Schaeffer, C. M. Lewis, P. L. Schwartzberg

Research output: Contribution to journalArticle

Abstract

The Tec kinases have been implicated as important components of signalling pathways downstream of lymphocyte antigen receptors. Activation of these kinases requires two steps: (i) phosphorylation by Src family kinases and (ii) plasma membrane localization, which is mediated by interaction between the pleckstrin homology (PH) domains of Tec kinases and the products of phosphoinositide-3 kinase (PI-3K). Irk and Rlk/Txk are Tec kinases expressed in T-lymphocytes. Despite similarity to other Tec kinases, Rlk/Txk lacks a PH domain and instead possesses a palmitoylated cysteine-string motif. We have found that both Rlk/Txk and Itk are phosphorylated in response to T-cell receptor stimulation and can be activated by phosphorylation by Src family kinases. However, consistent with its lack of PH domain, Rlk/Txk is phosphorylated independent of PI-3K activity. Furthermore, we demonstrated that like Itk, Rlk/Txk is associated with lipid RAFTs (detergent-insoluble, cholesterol-rich regions of the membrane), but unlike Itk, Rlk/Txk's RAFT association is independent of PI-3K activity. Despite these differences, Rlk/Txk partially compensates for loss of Itk in gene-targeted animals, suggesting overlapping functions for these kinases.

Original languageEnglish (US)
Pages (from-to)863-867
Number of pages5
JournalBiochemical Society Transactions
Volume29
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Phosphatidylinositol 3-kinase
  • RAFTs
  • T lymphocytes
  • Tyrosine kinase

ASJC Scopus subject areas

  • Biochemistry

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  • Cite this

    Czar, M. J., Debnath, J., Schaeffer, E. M., Lewis, C. M., & Schwartzberg, P. L. (2001). Biochemical and genetic analyses of the Tec kinases Itk and Rlk/Txk. Biochemical Society Transactions, 29(6), 863-867. https://doi.org/10.1042/0300-5127:0290863