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Gene Review

Txk  -  TXK tyrosine kinase

Mus musculus

Synonyms: A130089B16Rik, Btkl, PTK-RL-18, PTK4, Resting lymphocyte kinase, ...
 
 
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Disease relevance of Txk

  • A novel T cell-specific adaptor protein, RIBP, was identified based on its ability to bind Rlk/Txk in a yeast two-hybrid screen of a mouse T cell lymphoma library [1].
 

High impact information on Txk

  • Three members of this family, Itk, Rlk, and Tec, are expressed in T cells and activated in response to T cell receptor (TCR) engagement [2].
  • These data indicate a critical role for Itk and Rlk in conventional CD8(+) T cell development in the thymus [3].
  • The Tec family tyrosine kinases Itk and Rlk regulate the development of conventional CD8+ T cells [3].
  • We show here that the mutation of Rlk and Itk impaired activation of the transcription factors NFAT and AP-1 and production of both T helper type 1 (TH1) and TH2 cytokines [4].
  • Txk, a Tec family protein tyrosine kinase, is expressed in both immature and mature T cells and in mast cells [5].
 

Biological context of Txk

  • Txk also restored PLCgamma2/calcium signaling but, unlike other Tec kinases, functioned in a phosphatidylinositol 3-kinase-independent manner and failed to reconstitute apoptosis [6].
  • We have identified a 62-kDa murine protein tyrosine kinase predominantly expressed within the T cell lineage, which we have termed Rlk (for Resting lymphocyte kinase). rlk mRNA was found to be expressed in the fetal thymus as early as day 13 of embryonic development as well as in adult thymus and mature resting peripheral T cells [7].
  • Conversely, in the itk(+/+) (wild-type) background, overexpression of Txk inhibited positive selection of TCR transgenic thymocytes, presumably due to induction of cell death [5].
  • By overexpressing Txk in T cells throughout development, we found that Txk specifically augments the phospholipase C (PLC)-gamma1-mediated calcium signal transduction pathway upon T cell antigen receptor (TCR) engagement [5].
  • The genomic organization of Txk consists of 15 exons with strong exon-intron organizational homology to Btk, the only other Tec-family kinase for which the genomic structure is fully known [8].
 

Anatomical context of Txk

 

Associations of Txk with chemical compounds

 

Other interactions of Txk

 

Analytical, diagnostic and therapeutic context of Txk

References

  1. RIBP, a novel Rlk/Txk- and itk-binding adaptor protein that regulates T cell activation. Rajagopal, K., Sommers, C.L., Decker, D.C., Mitchell, E.O., Korthauer, U., Sperling, A.I., Kozak, C.A., Love, P.E., Bluestone, J.A. J. Exp. Med. (1999) [Pubmed]
  2. Tec family kinases in T lymphocyte development and function. Berg, L.J., Finkelstein, L.D., Lucas, J.A., Schwartzberg, P.L. Annu. Rev. Immunol. (2005) [Pubmed]
  3. The Tec family tyrosine kinases Itk and Rlk regulate the development of conventional CD8+ T cells. Atherly, L.O., Lucas, J.A., Felices, M., Yin, C.C., Reiner, S.L., Berg, L.J. Immunity (2006) [Pubmed]
  4. Mutation of Tec family kinases alters T helper cell differentiation. Schaeffer, E.M., Yap, G.S., Lewis, C.M., Czar, M.J., McVicar, D.W., Cheever, A.W., Sher, A., Schwartzberg, P.L. Nat. Immunol. (2001) [Pubmed]
  5. A role for the Tec family tyrosine kinase Txk in T cell activation and thymocyte selection. Sommers, C.L., Rabin, R.L., Grinberg, A., Tsay, H.C., Farber, J., Love, P.E. J. Exp. Med. (1999) [Pubmed]
  6. Reconstitution of Btk signaling by the atypical tec family tyrosine kinases Bmx and Txk. Tomlinson, M.G., Kurosaki, T., Berson, A.E., Fujii, G.H., Johnston, J.A., Bolen, J.B. J. Biol. Chem. (1999) [Pubmed]
  7. Identification of Rlk, a novel protein tyrosine kinase with predominant expression in the T cell lineage. Hu, Q., Davidson, D., Schwartzberg, P.L., Macchiarini, F., Lenardo, M.J., Bluestone, J.A., Matis, L.A. J. Biol. Chem. (1995) [Pubmed]
  8. Human Txk: genomic organization, structure and contiguous physical linkage with the Tec gene. Ohta, Y., Haire, R.N., Amemiya, C.T., Litman, R.T., Träger, T., Riess, O., Litman, G.W. Oncogene (1996) [Pubmed]
  9. Murine txk: a protein tyrosine kinase gene regulated by T cell activation. Sommers, C.L., Huang, K., Shores, E.W., Grinberg, A., Charlick, D.A., Kozak, C.A., Love, P.E. Oncogene (1995) [Pubmed]
  10. Determinants of intra versus intermolecular self-association within the regulatory domains of Rlk and Itk. Laederach, A., Cradic, K.W., Fulton, D.B., Andreotti, A.H. J. Mol. Biol. (2003) [Pubmed]
  11. rlk/TXK encodes two forms of a novel cysteine string tyrosine kinase activated by Src family kinases. Debnath, J., Chamorro, M., Czar, M.J., Schaeffer, E.M., Lenardo, M.J., Varmus, H.E., Schwartzberg, P.L. Mol. Cell. Biol. (1999) [Pubmed]
  12. Th1-dominant shift of T cell cytokine production, and subsequent reduction of serum immunoglobulin E response by administration in vivo of plasmid expressing Txk/Rlk, a member of Tec family tyrosine kinases, in a mouse model. Takeno, M., Yoshikawa, H., Kurokawa, M., Takeba, Y., Kashiwakura, J.I., Sakaguchi, M., Yasueda, H., Suzuki, N. Clin. Exp. Allergy (2004) [Pubmed]
 
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