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 language | English (US) |
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Pages (from-to) | 863-867 |
Number of pages | 5 |
Journal | Biochemical Society Transactions |
Volume | 29 |
Issue number | 6 |
DOIs | |
State | Published - 2001 |
Externally published | Yes |
Keywords
- Phosphatidylinositol 3-kinase
- RAFTs
- T lymphocytes
- Tyrosine kinase
ASJC Scopus subject areas
- Biochemistry