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ITK (gene)

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ITK (gene)

IL2-inducible T-cell kinase
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; EMT; LPFS1; LYK; PSCTK2
External IDs ChEMBL: GeneCards:
EC number
RNA expression pattern
Protein domains
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

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]

Contents

  • Function 1
  • Structure 2
  • Interactions 3
  • References 4
  • Further reading 5

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]

Structure

This protein contains the following domains, which are often found in intracellular kinases:[5]

Interactions

ITK (gene) has been shown to interact with:

References

  1. ^ 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.  
  2. ^ a b Gomez-Rodriguez J, Kraus ZJ, Schwartzberg PL (March 2011). "Tec family kinases Itk and Rlk / Txk in T lymphocytes: cross-regulation of cytokine production and T-cell fates.". FEBS 278 (12): 1980–1989.  
  3. ^ Kosaka Y, Felices M, Berg LJ (October 2006). "Itk and Th2 responses: action but no reaction". Trends Immunol. 27 (10): 453–60.  
  4. ^ "Entrez Gene: ITK IL2-inducible T-cell kinase". 
  5. ^ 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.  
  6. ^ a b c Bunnell SC, Diehn M, Yaffe MB, Findell PR, Cantley LC, Berg LJ (2000). "Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade". J. Biol. Chem. 275 (3): 2219–30.  
  7. ^ a b c Bunnell SC, Henry PA, Kolluri R, Kirchhausen T, Rickles RJ, Berg LJ (1996). "Identification of Itk/Tsk Src homology 3 domain ligands". J. Biol. Chem. 271 (41): 25646–56.  
  8. ^ a b Andreotti AH, Bunnell SC, Feng S, Berg LJ, Schreiber SL (1997). "Regulatory intramolecular association in a tyrosine kinase of the Tec family". Nature 385 (6611): 93–7.  
  9. ^ a b Hao S, August A (2002). "The proline rich region of the Tec homology domain of ITK regulates its activity". FEBS Lett. 525 (1-3): 53–8.  
  10. ^ Perez-Villar JJ, O'Day K, Hewgill DH, Nadler SG, Kanner SB (2001). "Nuclear localization of the tyrosine kinase Itk and interaction of its SH3 domain with karyopherin alpha (Rch1alpha)". Int. Immunol. 13 (10): 1265–74.  
  11. ^ 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.  
  12. ^ Perez-Villar JJ, Whitney GS, Sitnick MT, Dunn RJ, Venkatesan S, O'Day K, Schieven GL, Lin TA, Kanner SB (2002). "Phosphorylation of the linker for activation of T-cells by Itk promotes recruitment of Vav". Biochemistry 41 (34): 10732–40.  
  13. ^ Shim EK, Moon CS, Lee GY, Ha YJ, Chae SK, Lee JR (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. 575 (1-3): 35–40.  
  14. ^ Perez-Villar JJ, Kanner SB (1999). "Regulated association between the tyrosine kinase Emt/Itk/Tsk and phospholipase-C gamma 1 in human T lymphocytes". J. Immunol. 163 (12): 6435–41.  
  15. ^ Brazin KN, Mallis RJ, Fulton DB, Andreotti AH (2002). "Regulation of the tyrosine kinase Itk by the peptidyl-prolyl isomerase cyclophilin A". Proc. Natl. Acad. Sci. U.S.A. 99 (4): 1899–904.  
  16. ^ Cory GO, MacCarthy-Morrogh L, Banin S, Gout I, Brickell PM, Levinsky RJ, Kinnon C, Lovering RC (1996). "Evidence that the Wiskott-Aldrich syndrome protein may be involved in lymphoid cell signaling pathways". J. Immunol. 157 (9): 3791–5.  

Further reading

  • Kosaka Y, Felices M, Berg LJ (2006). "Itk and Th2 responses: action but no reaction.". Trends Immunol. 27 (10): 453–60.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • Hawkins J, Marcy A (2001). "Characterization of Itk tyrosine kinase: contribution of noncatalytic domains to enzymatic activity.". Protein Expr. Purif. 22 (2): 211–9.  


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