Biology:ITK (gene)
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Tyrosine-protein kinase ITK/TSK also known as interleukin-2-inducible T-cell kinase or simply ITK, is a protein that in humans is encoded by the ITK gene.[1] ITK is a member of the TEC family of kinases and is highly expressed in T cells.[2]
Function
This gene encodes an intracellular tyrosine kinase expressed in T-cells. The protein is thought to play a role in T-cell proliferation and differentiation.[3][4] ITK is functionally important for the development and effector function of Th2 and Th17 cells.[2]
Mice lacking ITK were shown to not be susceptible to asthma.[5]
Structure
This protein contains the following domains, which are often found in intracellular kinases:[6]
- N-terminus – PH (pleckstrin homology domain)
- TH – Tec family homology domain (including Bruton's tyrosine kinase Cys-rich motif and Proline rich region)
- SH3 – (Src homology 3)
- SH2 – (Src homology 2)
- C-terminus – tyrosine kinase, catalytic domain
Interactions
ITK (gene) has been shown to interact with:
- FYN,[7][8]
- Grb2[7][9] and
- KHDRBS1,[8][9][10]
- KPNA2,[11]
- LAT,[12][13]
- LCP2,[7][14]
- PLCG1,[10][15]
- PPIA,[16] and
- WAS.[8][17]
References
- ↑ "Identification, cloning, and characterization of a novel human T-cell-specific tyrosine kinase located at the hematopoietin complex on chromosome 5q". Blood 82 (5): 1561–72. September 1993. doi:10.1182/blood.V82.5.1561.1561. PMID 8364206. http://bloodjournal.hematologylibrary.org/cgi/content/abstract/bloodjournal;82/5/1561.
- ↑ 2.0 2.1 "Tec family kinases Itk and Rlk/Txk in T lymphocytes: cross-regulation of cytokine production and T-cell fates.". FEBS 278 (12): 1980–1989. March 2011. doi:10.1111/j.1742-4658.2011.08072.x. PMID 21362139.
- ↑ "Itk and Th2 responses: action but no reaction". Trends Immunol. 27 (10): 453–60. October 2006. doi:10.1016/j.it.2006.08.006. PMID 16931156.
- ↑ "Entrez Gene: ITK IL2-inducible T-cell kinase". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3702.
- ↑ Mueller, Cynthia; August, Avery (2003-05-15). "Attenuation of immunological symptoms of allergic asthma in mice lacking the tyrosine kinase ITK". Journal of Immunology 170 (10): 5056–5063. doi:10.4049/jimmunol.170.10.5056. ISSN 0022-1767. PMID 12734350.
- ↑ "Characterization of Itk tyrosine kinase: contribution of noncatalytic domains to enzymatic activity". Protein Expr. Purif. 22 (2): 211–9. July 2001. doi:10.1006/prep.2001.1447. PMID 11437596.
- ↑ 7.0 7.1 7.2 "Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade". J. Biol. Chem. 275 (3): 2219–30. 2000. doi:10.1074/jbc.275.3.2219. PMID 10636929.
- ↑ 8.0 8.1 8.2 "Identification of Itk/Tsk Src homology 3 domain ligands". J. Biol. Chem. 271 (41): 25646–56. 1996. doi:10.1074/jbc.271.41.25646. PMID 8810341.
- ↑ 9.0 9.1 "Regulatory intramolecular association in a tyrosine kinase of the Tec family". Nature 385 (6611): 93–7. 1997. doi:10.1038/385093a0. PMID 8985255. Bibcode: 1997Natur.385...93A.
- ↑ 10.0 10.1 "The proline rich region of the Tec homology domain of ITK regulates its activity". FEBS Lett. 525 (1–3): 53–8. 2002. doi:10.1016/S0014-5793(02)03066-1. PMID 12163161.
- ↑ "Nuclear localization of the tyrosine kinase Itk and interaction of its SH3 domain with karyopherin alpha (Rch1alpha)". Int. Immunol. 13 (10): 1265–74. 2001. doi:10.1093/intimm/13.10.1265. PMID 11581171.
- ↑ "Itk/Emt/Tsk activation in response to CD3 cross-linking in Jurkat T cells requires ZAP-70 and Lat and is independent of membrane recruitment". J. Biol. Chem. 274 (41): 29323–30. 1999. doi:10.1074/jbc.274.41.29323. PMID 10506192.
- ↑ "Phosphorylation of the linker for activation of T-cells by Itk promotes recruitment of Vav". Biochemistry 41 (34): 10732–40. 2002. doi:10.1021/bi025554o. PMID 12186560.
- ↑ "Association of the Src homology 2 domain-containing leukocyte phosphoprotein of 76 kD (SLP-76) with the p85 subunit of phosphoinositide 3-kinase". FEBS Lett. 575 (1–3): 35–40. 2004. doi:10.1016/j.febslet.2004.07.090. PMID 15388330.
- ↑ "Regulated association between the tyrosine kinase Emt/Itk/Tsk and phospholipase-C gamma 1 in human T lymphocytes". J. Immunol. 163 (12): 6435–41. 1999. doi:10.4049/jimmunol.163.12.6435. PMID 10586033.
- ↑ "Regulation of the tyrosine kinase Itk by the peptidyl-prolyl isomerase cyclophilin A". Proc. Natl. Acad. Sci. U.S.A. 99 (4): 1899–904. 2002. doi:10.1073/pnas.042529199. PMID 11830645. Bibcode: 2002PNAS...99.1899B.
- ↑ "Evidence that the Wiskott-Aldrich syndrome protein may be involved in lymphoid cell signaling pathways". J. Immunol. 157 (9): 3791–5. 1996. doi:10.4049/jimmunol.157.9.3791. PMID 8892607.
Further reading
- "Itk and Th2 responses: action but no reaction.". Trends Immunol. 27 (10): 453–60. 2006. doi:10.1016/j.it.2006.08.006. PMID 16931156.
- "Mapping of the gene for the tyrosine kinase Itk to a region of conserved synteny between mouse chromosome 11 and human chromosome 5q.". Genomics 23 (1): 269–71. 1995. doi:10.1006/geno.1994.1492. PMID 7829087.
- "Identification, cloning, and characterization of a novel human T-cell-specific tyrosine kinase located at the hematopoietin complex on chromosome 5q.". Blood 82 (5): 1561–72. 1993. doi:10.1182/blood.V82.5.1561.1561. PMID 8364206.
- "A novel human tyrosine kinase gene inducible in T cells by interleukin 2.". FEBS Lett. 324 (1): 1–5. 1993. doi:10.1016/0014-5793(93)81520-A. PMID 8504851.
- "Identification of Itk/Tsk Src homology 3 domain ligands.". J. Biol. Chem. 271 (41): 25646–56. 1996. doi:10.1074/jbc.271.41.25646. PMID 8810341.
- "Regulatory intramolecular association in a tyrosine kinase of the Tec family.". Nature 385 (6611): 93–7. 1997. doi:10.1038/385093a0. PMID 8985255. Bibcode: 1997Natur.385...93A.
- "Lck phosphorylates the activation loop tyrosine of the Itk kinase domain and activates Itk kinase activity.". J. Biol. Chem. 272 (40): 25401–8. 1997. doi:10.1074/jbc.272.40.25401. PMID 9312162.
- "Human Emt tyrosine kinase is specifically expressed both in mature T-lymphocytes and T-cell associated hematopoietic malignancies.". Leuk. Lymphoma 32 (5–6): 513–22. 1999. doi:10.3109/10428199909058409. PMID 10048424.
- "Itk/Emt/Tsk activation in response to CD3 cross-linking in Jurkat T cells requires ZAP-70 and Lat and is independent of membrane recruitment.". J. Biol. Chem. 274 (41): 29323–30. 1999. doi:10.1074/jbc.274.41.29323. PMID 10506192.
- "Interaction of SLP adaptors with the SH2 domain of Tec family kinases.". Eur. J. Immunol. 29 (11): 3702–11. 1999. doi:10.1002/(SICI)1521-4141(199911)29:11<3702::AID-IMMU3702>3.0.CO;2-R. PMID 10556826.
- "Regulated association between the tyrosine kinase Emt/Itk/Tsk and phospholipase-C gamma 1 in human T lymphocytes.". J. Immunol. 163 (12): 6435–41. 2000. doi:10.4049/jimmunol.163.12.6435. PMID 10586033.
- "RIBP, a novel Rlk/Txk- and itk-binding adaptor protein that regulates T cell activation.". J. Exp. Med. 190 (11): 1657–68. 2000. doi:10.1084/jem.190.11.1657. PMID 10587356.
- "Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade.". J. Biol. Chem. 275 (3): 2219–30. 2000. doi:10.1074/jbc.275.3.2219. PMID 10636929.
- "Deficiency of PTEN in Jurkat T cells causes constitutive localization of Itk to the plasma membrane and hyperresponsiveness to CD3 stimulation.". Mol. Cell. Biol. 20 (18): 6945–57. 2000. doi:10.1128/MCB.20.18.6945-6957.2000. PMID 10958690.
- "Characterization of Itk tyrosine kinase: contribution of noncatalytic domains to enzymatic activity.". Protein Expr. Purif. 22 (2): 211–9. 2001. doi:10.1006/prep.2001.1447. PMID 11437596.
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