ITK (gene)

IL2-inducible T-cell kinase
	; 1LUI
Available structures
PDB	1SM2, 1SNU, 1SNX, 2E6I, 2YUQ, 3MIY, 3MJ1, 3MJ2
Identifiers
Symbols	ITK; EMT; LYK; MGC126257; MGC126258; PSCTK2
External IDs	OMIM: 186973 MGI: 96621 HomoloGene: 4051 GeneCards: ITK Gene
EC number	2.7.10.2
Gene Ontology
Molecular function	• nucleotide binding; • non-membrane spanning protein tyrosine kinase activity; • protein binding; • ATP binding; • metal ion binding;
Cellular component	• cytoplasm; • cytosol;
Biological process	• cytokine production; • NK T cell differentiation; • adaptive immune response; • cellular defense response; • signal transduction; • activation of phospholipase C activity; • interferon-gamma production; • interleukin-4 production; • intracellular signal transduction; • T cell activation; • T cell receptor signaling pathway; • T cell receptor signaling pathway;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Protein domains
Orthologs
	This box: view; talk; edit;

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IL2-inducible T-cell kinase, also known as ITK, is a protein that in humans is encoded by the ITK gene.^[1]

[edit] 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.^[2]^[3]

[edit] Structure

This protein contains the following domains, which are often found in intracellular kinases:^[4]

N-terminus – PH (pleckstrin homology domain)
BTK – Bruton's tyrosine kinase Cys-rich motif
SH3 – (Src homology 3)
SH2 – (Src homology 2)
C-terminus – tyrosine kinase, catalytic domain

[edit] Interactions

ITK (gene) has been shown to interact with FYN,^[5]^[6] Wiskott-Aldrich syndrome protein,^[7]^[6] KHDRBS1,^[8]^[9]^[6] PLCG1,^[10]^[8] Lymphocyte cytosolic protein 2,^[11]^[5] Linker of activated T cells,^[12]^[13] Karyopherin alpha 2,^[14] Grb2^[5]^[9] and Peptidylprolyl isomerase A.^[15]

[edit] References

^ Gibson S, Leung B, Squire JA, Hill M, Arima N, Goss P, Hogg D, Mills GB (September 1993). "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. PMID 8364206. http://bloodjournal.hematologylibrary.org/cgi/content/abstract/bloodjournal;82/5/1561.
^ Kosaka Y, Felices M, Berg LJ (October 2006). "Itk and Th2 responses: action but no reaction". Trends Immunol. 27 (10): 453–60. doi:10.1016/j.it.2006.08.006. PMID 16931156.
^ "Entrez Gene: ITK IL2-inducible T-cell kinase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3702.
^ Hawkins J, Marcy A (July 2001). "Characterization of Itk tyrosine kinase: contribution of noncatalytic domains to enzymatic activity". Protein Expr. Purif. 22 (2): 211–9. doi:10.1006/prep.2001.1447. PMID 11437596.
^ ^a ^b ^c Bunnell, S C; Diehn M, Yaffe M B, Findell P R, Cantley L C, Berg L J (Jan. 2000). "Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade". J. Biol. Chem. (UNITED STATES) 275 (3): 2219–30. doi:10.1074/jbc.275.3.2219. ISSN 0021-9258. PMID 10636929.
^ ^a ^b ^c Bunnell, S C; Henry P A, Kolluri R, Kirchhausen T, Rickles R J, Berg L J (Oct. 1996). "Identification of Itk/Tsk Src homology 3 domain ligands". J. Biol. Chem. (UNITED STATES) 271 (41): 25646–56. doi:10.1074/jbc.271.41.25646. ISSN 0021-9258. PMID 8810341.
^ Cory, G O; MacCarthy-Morrogh L, Banin S, Gout I, Brickell P M, Levinsky R J, Kinnon C, Lovering R C (Nov. 1996). "Evidence that the Wiskott-Aldrich syndrome protein may be involved in lymphoid cell signaling pathways". J. Immunol. (UNITED STATES) 157 (9): 3791–5. ISSN 0022-1767. PMID 8892607.
^ ^a ^b Hao, Shengli; August Avery (Aug. 2002). "The proline rich region of the Tec homology domain of ITK regulates its activity". FEBS Lett. (Netherlands) 525 (1-3): 53–8. doi:10.1016/S0014-5793(02)03066-1. ISSN 0014-5793. PMID 12163161.
^ ^a ^b Andreotti, A H; Bunnell S C, Feng S, Berg L J, Schreiber S L (Jan. 1997). "Regulatory intramolecular association in a tyrosine kinase of the Tec family". Nature (ENGLAND) 385 (6611): 93–7. doi:10.1038/385093a0. ISSN 0028-0836. PMID 8985255.
^ Perez-Villar, J J; Kanner S B (Dec. 1999). "Regulated association between the tyrosine kinase Emt/Itk/Tsk and phospholipase-C gamma 1 in human T lymphocytes". J. Immunol. (UNITED STATES) 163 (12): 6435–41. ISSN 0022-1767. PMID 10586033.
^ Shim, Eun Kyung; Moon Chang Suk, Lee Gi Yeon, Ha Yun Jung, Chae Suhn-Kee, Lee Jong Ran (Sep. 2004). "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. (Netherlands) 575 (1-3): 35–40. doi:10.1016/j.febslet.2004.07.090. ISSN 0014-5793. PMID 15388330.
^ Shan, X; Wange R L (Oct. 1999). "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. (UNITED STATES) 274 (41): 29323–30. doi:10.1074/jbc.274.41.29323. ISSN 0021-9258. PMID 10506192.
^ Perez-Villar, Juan J; Whitney Gena S, Sitnick Mitchell T, Dunn Robert J, Venkatesan Srividhya, O'Day Kathleen, Schieven Gary L, Lin Tai-An, Kanner Steven B (Aug. 2002). "Phosphorylation of the linker for activation of T-cells by Itk promotes recruitment of Vav". Biochemistry (United States) 41 (34): 10732–40. doi:10.1021/bi025554o. ISSN 0006-2960. PMID 12186560.
^ Perez-Villar, J J; O'Day K, Hewgill D H, Nadler S G, Kanner S B (Oct. 2001). "Nuclear localization of the tyrosine kinase Itk and interaction of its SH3 domain with karyopherin alpha (Rch1alpha)". Int. Immunol. (England) 13 (10): 1265–74. doi:10.1093/intimm/13.10.1265. ISSN 0953-8178. PMID 11581171.
^ Brazin, Kristine N; Mallis Robert J, Fulton D Bruce, Andreotti Amy H (Feb. 2002). "Regulation of the tyrosine kinase Itk by the peptidyl-prolyl isomerase cyclophilin A". Proc. Natl. Acad. Sci. U.S.A. (United States) 99 (4): 1899–904. doi:10.1073/pnas.042529199. ISSN 0027-8424. PMC 122291. PMID 11830645. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=122291.

[edit] Further reading

Kosaka Y, Felices M, Berg LJ (2006). "Itk and Th2 responses: action but no reaction.". Trends Immunol. 27 (10): 453–60. doi:10.1016/j.it.2006.08.006. PMID 16931156.
Janis EM, Siliciano JD, Isaac DD, et al. (1995). "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. doi:10.1006/geno.1994.1492. PMID 7829087.
Gibson S, Leung B, Squire JA, et al. (1993). "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. PMID 8364206.
Tanaka N, Asao H, Ohtani K, et al. (1993). "A novel human tyrosine kinase gene inducible in T cells by interleukin 2.". FEBS Lett. 324 (1): 1–5. doi:10.1016/0014-5793(93)81520-A. PMID 8504851.
Bunnell SC, Henry PA, Kolluri R, et al. (1996). "Identification of Itk/Tsk Src homology 3 domain ligands.". J. Biol. Chem. 271 (41): 25646–56. doi:10.1074/jbc.271.41.25646. PMID 8810341.
Andreotti AH, Bunnell SC, Feng S, et al. (1997). "Regulatory intramolecular association in a tyrosine kinase of the Tec family.". Nature 385 (6611): 93–7. doi:10.1038/385093a0. PMID 8985255.
Heyeck SD, Wilcox HM, Bunnell SC, Berg LJ (1997). "Lck phosphorylates the activation loop tyrosine of the Itk kinase domain and activates Itk kinase activity.". J. Biol. Chem. 272 (40): 25401–8. doi:10.1074/jbc.272.40.25401. PMID 9312162.
Kaukonen J, Savolainen ER, Palotie A (1999). "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. doi:10.3109/10428199909058409. PMID 10048424.
Shan X, Wange RL (1999). "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. doi:10.1074/jbc.274.41.29323. PMID 10506192.
Su YW, Zhang Y, Schweikert J, et al. (1999). "Interaction of SLP adaptors with the SH2 domain of Tec family kinases.". Eur. J. Immunol. 29 (11): 3702–11. doi:10.1002/(SICI)1521-4141(199911)29:11<3702::AID-IMMU3702>3.0.CO;2-R. PMID 10556826.
Perez-Villar JJ, Kanner SB (2000). "Regulated association between the tyrosine kinase Emt/Itk/Tsk and phospholipase-C gamma 1 in human T lymphocytes.". J. Immunol. 163 (12): 6435–41. PMID 10586033.
Rajagopal K, Sommers CL, Decker DC, et al. (2000). "RIBP, a novel Rlk/Txk- and itk-binding adaptor protein that regulates T cell activation.". J. Exp. Med. 190 (11): 1657–68. doi:10.1084/jem.190.11.1657. PMC 2195727. PMID 10587356. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2195727.
Bunnell SC, Diehn M, Yaffe MB, et al. (2000). "Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade.". J. Biol. Chem. 275 (3): 2219–30. doi:10.1074/jbc.275.3.2219. PMID 10636929.
Shan X, Czar MJ, Bunnell SC, et al. (2000). "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. doi:10.1128/MCB.20.18.6945-6957.2000. PMC 88770. PMID 10958690. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=88770.
Hawkins J, Marcy A (2001). "Characterization of Itk tyrosine kinase: contribution of noncatalytic domains to enzymatic activity.". Protein Expr. Purif. 22 (2): 211–9. doi:10.1006/prep.2001.1447. PMID 11437596.

This article on a gene on chromosome 5 is a stub. You can help Wikipedia by expanding it.

[pmid8364206-0] Gibson S, Leung B, Squire JA, Hill M, Arima N, Goss P, Hogg D, Mills GB (September 1993). "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. PMID 8364206. http://bloodjournal.hematologylibrary.org/cgi/content/abstract/bloodjournal;82/5/1561.

[pmid16931156-1] Kosaka Y, Felices M, Berg LJ (October 2006). "Itk and Th2 responses: action but no reaction". Trends Immunol. 27 (10): 453–60. doi:10.1016/j.it.2006.08.006. PMID 16931156.

[2] "Entrez Gene: ITK IL2-inducible T-cell kinase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3702.

[pmid11437596-3] Hawkins J, Marcy A (July 2001). "Characterization of Itk tyrosine kinase: contribution of noncatalytic domains to enzymatic activity". Protein Expr. Purif. 22 (2): 211–9. doi:10.1006/prep.2001.1447. PMID 11437596.

[pmid10636929-4] Bunnell, S C; Diehn M, Yaffe M B, Findell P R, Cantley L C, Berg L J (Jan. 2000). "Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade". J. Biol. Chem. (UNITED STATES) 275 (3): 2219–30. doi:10.1074/jbc.275.3.2219. ISSN 0021-9258. PMID 10636929.

[pmid8810341-5] Bunnell, S C; Henry P A, Kolluri R, Kirchhausen T, Rickles R J, Berg L J (Oct. 1996). "Identification of Itk/Tsk Src homology 3 domain ligands". J. Biol. Chem. (UNITED STATES) 271 (41): 25646–56. doi:10.1074/jbc.271.41.25646. ISSN 0021-9258. PMID 8810341.

[pmid8892607-6] Cory, G O; MacCarthy-Morrogh L, Banin S, Gout I, Brickell P M, Levinsky R J, Kinnon C, Lovering R C (Nov. 1996). "Evidence that the Wiskott-Aldrich syndrome protein may be involved in lymphoid cell signaling pathways". J. Immunol. (UNITED STATES) 157 (9): 3791–5. ISSN 0022-1767. PMID 8892607.

[pmid12163161-7] Hao, Shengli; August Avery (Aug. 2002). "The proline rich region of the Tec homology domain of ITK regulates its activity". FEBS Lett. (Netherlands) 525 (1-3): 53–8. doi:10.1016/S0014-5793(02)03066-1. ISSN 0014-5793. PMID 12163161.

[pmid8985255-8] Andreotti, A H; Bunnell S C, Feng S, Berg L J, Schreiber S L (Jan. 1997). "Regulatory intramolecular association in a tyrosine kinase of the Tec family". Nature (ENGLAND) 385 (6611): 93–7. doi:10.1038/385093a0. ISSN 0028-0836. PMID 8985255.

[pmid10586033-9] Perez-Villar, J J; Kanner S B (Dec. 1999). "Regulated association between the tyrosine kinase Emt/Itk/Tsk and phospholipase-C gamma 1 in human T lymphocytes". J. Immunol. (UNITED STATES) 163 (12): 6435–41. ISSN 0022-1767. PMID 10586033.

[pmid15388330-10] Shim, Eun Kyung; Moon Chang Suk, Lee Gi Yeon, Ha Yun Jung, Chae Suhn-Kee, Lee Jong Ran (Sep. 2004). "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. (Netherlands) 575 (1-3): 35–40. doi:10.1016/j.febslet.2004.07.090. ISSN 0014-5793. PMID 15388330.

[pmid10506192-11] Shan, X; Wange R L (Oct. 1999). "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. (UNITED STATES) 274 (41): 29323–30. doi:10.1074/jbc.274.41.29323. ISSN 0021-9258. PMID 10506192.

[pmid12186560-12] Perez-Villar, Juan J; Whitney Gena S, Sitnick Mitchell T, Dunn Robert J, Venkatesan Srividhya, O'Day Kathleen, Schieven Gary L, Lin Tai-An, Kanner Steven B (Aug. 2002). "Phosphorylation of the linker for activation of T-cells by Itk promotes recruitment of Vav". Biochemistry (United States) 41 (34): 10732–40. doi:10.1021/bi025554o. ISSN 0006-2960. PMID 12186560.

[pmid11581171-13] Perez-Villar, J J; O'Day K, Hewgill D H, Nadler S G, Kanner S B (Oct. 2001). "Nuclear localization of the tyrosine kinase Itk and interaction of its SH3 domain with karyopherin alpha (Rch1alpha)". Int. Immunol. (England) 13 (10): 1265–74. doi:10.1093/intimm/13.10.1265. ISSN 0953-8178. PMID 11581171.

[pmid11830645-14] Brazin, Kristine N; Mallis Robert J, Fulton D Bruce, Andreotti Amy H (Feb. 2002). "Regulation of the tyrosine kinase Itk by the peptidyl-prolyl isomerase cyclophilin A". Proc. Natl. Acad. Sci. U.S.A. (United States) 99 (4): 1899–904. doi:10.1073/pnas.042529199. ISSN 0027-8424. PMC 122291. PMID 11830645. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=122291.

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ITK (gene)

Contents

[edit] Function

[edit] Structure

[edit] Interactions

[edit] References

[edit] Further reading

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