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Gene Review

IARS  -  isoleucyl-tRNA synthetase

Homo sapiens

Synonyms: IARS1, ILERS, ILRS, IRS, IleRS, ...
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Disease relevance of IARS

  • Because human IRS has previously been shown to be the target of antibodies in autoimmune disease, we discuss the role of protein structural features in the development of an autoimmune response to IRS [1].
  • The efficacy of a biocompatible, surgically implantable, antimicrobial release system (IARS) as the exclusive antimicrobial therapy of necrotizing external otitis (NEO) was evaluated in six NEO patients [2].
  • Preliminary analyses of treatment results and prognostic factors from the first Intergroup Rhabdomyosarcoma Study (IRS I) suggested that alveolar histology and extremity site were among factors associated with an adverse outcome in clinical group I patients whose tumors had been completely resected [3].
  • Both of the IRS proteins modulate VPF/VEGF expression in pancreatic cancer cells by different mechanistic pathways [4].
  • Additionally, we studied birthweight as a predictor of the clustering of diseases associated with the IRS, defined as any two or more of the following conditions: hypertension, NIDDM or impaired glucose tolerance, dyslipidaemia [5].

Psychiatry related information on IARS

  • This study was carried out to examine the effects of immunochemotherapy with IL-2 and IFNalpha, alone and together, in cancer patients on serum DPP IV activity in relation to changes in depressive symptoms and the IRS [6].
  • The results suggest that: (i) alpha2-AR density is sensitive to graded differences in stress-induced anxiety; and (ii) psychological stress is accompanied by intertwined responses in the catecholaminergic system, such as alpha2-ARs, and the IRS, such as Th1/Th2-like functions and the production of TNFalpha [7].
  • Recently, however, it has been shown that depression and anxiety disorders are accompanied by activation of the inflammatory response system (IRS) [8].
  • BACKGROUND: Recently it has been reported that activation of the inflammatory response system (IRS) may play a role in the aging process and in the pathogenesis of the degenerative changes associated with Alzheimer's disease (SDAT) [9].
  • However, no research has examined the IRS in somatization disorder [10].

High impact information on IARS

  • Receptor-mediated phosphorylation of the IRS proteins is required for the propagation of signals for mitogenesis, glucose transport, and numerous other biological and biochemical events during insulin signaling [11].
  • Insulin signal transduction and the IRS proteins [11].
  • We make use of the newly defined metropolitan and micropolitan Core-Based Statistical Areas (CBSAs) and a seven-level size typology to tabulate origin-destination-specific migration flow data from both Census 2000 and IRS tax-return administrative records for the period 1995-2000 [12].
  • A chimeric peptide, p21-IRS, consisting of the carboxyl terminal domain of p21 conjugated to a pentapeptide (RYIRS) rapidly enters lymphoid cells and activates apoptosis [13].
  • PURPOSE: This study was performed to determine the incidence and risk factors involved in the development of a second malignant neoplasm (SMN) after treatment of primary rhabdomyosarcoma (RMS) in patients enrolled onto Intergroup Rhabdomyosarcoma Studies I and II (IRS I and II) [14].

Chemical compound and disease context of IARS


Biological context of IARS


Anatomical context of IARS

  • While most receptor tyrosine kinases signal by recruiting SH2 proteins directly to phosphorylation sites on their plasma membrane receptor, the insulin receptor phosphorylates intermediary IRS proteins that are distributed between the cytoplasm and a state of loose association with intracellular membranes [21].
  • In addition, we found that the IRS/PI 3'-K pathway is, at least in part, responsible for the prevention of apoptosis by IL-4 in normal splenic B cell cultures [22].
  • CONCLUSIONS/INTERPRETATION: The affinity of the PH domain for the phospholipids in the plasma membrane seems to influence the receptor-substrate interaction required for IRS tyrosine phosphorylation, indicating that the PH domain and the PTB domain of IRSs cooperatively function in insulin-stimulated tyrosine phosphorylation of these proteins [23].
  • Recent data indicate that low-birthweight adults are at a higher risk than their high-birthweight peers of developing ischemic heart disease or a cluster of conditions known as the IRS, which includes dyslipidaemias, hypertension, unfavorable body fat distribution and NIDDM [5].
  • RESULTS: Both univariable and multivariable analysis have shown that the COX-2 expression in human tumor epithelial cells was unrelated to overall patient survival and to disease-free survival, irrespectively of the cutoff point for IRS-COX2 [24].

Associations of IARS with chemical compounds

  • The best understood mechanism of IRS-protein-mediated signaling is the binding of SH2 domain-containing signaling molecules (such as PI 3'-kinase) by tyrosine phosphorylation sites on IRS proteins [11].
  • We conclude that aspirin may enhance insulin sensitivity by protecting IRS proteins from serine phosphorylation catalyzed by multiple kinases [25].
  • Our studies of multiple cell types in both mice and humans show the optimal IRS to contain a GGGG motif within the sequence, and the activity to require a phosphorothioate backbone [26].
  • Similarly, an alkaline solution of sodium oleate (pH 9.2) stimulated PBS but not IRS [15].
  • In this review, we use structural, evolutionary and functional analysis to divide PTB domains into three groups represented by phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like and phosphotyrosine-independent Dab-like PTBs, with the Dab-like PTB domains representing nearly 75% of proteins encoding PTB domains [27].

Analytical, diagnostic and therapeutic context of IARS


  1. Human isoleucyl-tRNA synthetase: sequence of the cDNA, alternative mRNA splicing, and the characteristics of an unusually long C-terminal extension. Nichols, R.C., Raben, N., Boerkoel, C.F., Plotz, P.H. Gene (1995) [Pubmed]
  2. Biocompatible implantable antimicrobial release for necrotizing external otitis. Ostfeld, E.J., Kupferberg, A. The Journal of laryngology and otology. (1991) [Pubmed]
  3. Results of intensive therapy in children with localized alveolar extremity rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study. Heyn, R., Beltangady, M., Hays, D., Lawrence, W., Newton, W., Crist, W., Tefft, M., Maurer, H.M. J. Clin. Oncol. (1989) [Pubmed]
  4. Role of insulin receptor substrates and protein kinase C-zeta in vascular permeability factor/vascular endothelial growth factor expression in pancreatic cancer cells. Neid, M., Datta, K., Stephan, S., Khanna, I., Pal, S., Shaw, L., White, M., Mukhopadhyay, D. J. Biol. Chem. (2004) [Pubmed]
  5. Birthweight and adult health outcomes in a biethnic population in the USA. Valdez, R., Athens, M.A., Thompson, G.H., Bradshaw, B.S., Stern, M.P. Diabetologia (1994) [Pubmed]
  6. Lowered serum dipeptidyl peptidase IV activity is associated with depressive symptoms and cytokine production in cancer patients receiving interleukin-2-based immunotherapy. Maes, M., Capuron, L., Ravaud, A., Gualde, N., Bosmans, E., Egyed, B., Dantzer, R., Neveu, P.J. Neuropsychopharmacology (2001) [Pubmed]
  7. Platelet alpha2-adrenoceptor density in humans: relationships to stress-induced anxiety, psychasthenic constitution, gender and stress-induced changes in the inflammatory response system. Maes, M., Van Gastel, A., Delmeire, L., Kenis, G., Bosmans, E., Song, C. Psychological medicine. (2002) [Pubmed]
  8. Immune activation in the early puerperium is related to postpartum anxiety and depressive symptoms. Maes, M., Lin, A.H., Ombelet, W., Stevens, K., Kenis, G., De Jongh, R., Cox, J., Bosmans, E. Psychoneuroendocrinology (2000) [Pubmed]
  9. Inflammatory markers in younger vs elderly normal volunteers and in patients with Alzheimer's disease. Maes, M., DeVos, N., Wauters, A., Demedts, P., Maurits, V.W., Neels, H., Bosmans, E., Altamura, C., Lin, A., Song, C., Vandenbroucke, M., Scharpe, S. Journal of psychiatric research. (1999) [Pubmed]
  10. Immunological differences between patients with major depression and somatization syndrome. Rief, W., Pilger, F., Ihle, D., Bosmans, E., Egyed, B., Maes, M. Psychiatry research. (2001) [Pubmed]
  11. Insulin signal transduction and the IRS proteins. Myers, M.G., White, M.F. Annu. Rev. Pharmacol. Toxicol. (1996) [Pubmed]
  12. Migration up and down the urban hierarchy and across the life course. Plane, D.A., Henrie, C.J., Perry, M.J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  13. A novel apoptosis pathway activated by the carboxyl terminus of p21. Dong, C., Li, Q., Lyu, S.C., Krensky, A.M., Clayberger, C. Blood (2005) [Pubmed]
  14. Second malignant neoplasms in children treated for rhabdomyosarcoma. Intergroup Rhabdomyosarcoma Study Committee. Heyn, R., Haeberlen, V., Newton, W.A., Ragab, A.H., Raney, R.B., Tefft, M., Wharam, M., Ensign, L.G., Maurer, H.M. J. Clin. Oncol. (1993) [Pubmed]
  15. Effects of a protein meal, intraduodenal HCl, and oleic acid on portal and peripheral venous secretin and on pancreatic bicarbonate secretion. Boden, G., Wilson, R.M., Essa-Koumar, N., Owen, O.E. Gut (1978) [Pubmed]
  16. Immunohistochemical determination of estrogen and progesterone receptor content in human breast cancer. Computer-assisted image analysis (QIC score) vs. subjective grading (IRS). Remmele, W., Schicketanz, K.H. Pathol. Res. Pract. (1993) [Pubmed]
  17. Tumor-cell DNA content predicts outcome in children and adolescents with clinical group III embryonal rhabdomyosarcoma. The Intergroup Rhabdomyosarcoma Study Committee of the Children's Cancer Group and the Pediatric Oncology Group. Pappo, A.S., Crist, W.M., Kuttesch, J., Rowe, S., Ashmun, R.A., Maurer, H.M., Newton, W.A., Asmar, L., Luo, X., Shapiro, D.N. J. Clin. Oncol. (1993) [Pubmed]
  18. Transactivation of ErbB2 and ErbB3 by tumor necrosis factor-alpha and anisomycin leads to impaired insulin signaling through serine/threonine phosphorylation of IRS proteins. Hemi, R., Paz, K., Wertheim, N., Karasik, A., Zick, Y., Kanety, H. J. Biol. Chem. (2002) [Pubmed]
  19. Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies. Shah, O.J., Wang, Z., Hunter, T. Curr. Biol. (2004) [Pubmed]
  20. Characterization of the interleukin-4 nuclear activated factor/STAT and its activation independent of the insulin receptor substrate proteins. Kotanides, H., Moczygemba, M., White, M.F., Reich, N.C. J. Biol. Chem. (1995) [Pubmed]
  21. Cellular compartmentalization in insulin action: altered signaling by a lipid-modified IRS-1. Kriauciunas, K.M., Myers, M.G., Kahn, C.R. Mol. Cell. Biol. (2000) [Pubmed]
  22. IL-4 protects cells from apoptosis via the insulin receptor substrate pathway and a second independent signaling pathway. Zamorano, J., Wang, H.Y., Wang, L.M., Pierce, J.H., Keegan, A.D. J. Immunol. (1996) [Pubmed]
  23. Insulin-independent and wortmannin-resistant targeting of IRS-3 to the plasma membrane via its pleckstrin homology domain mediates a different interaction with the insulin receptor from that of IRS-1. Kaburagi, Y., Satoh, S., Yamamoto-Honda, R., Ito, T., Ueki, K., Akanuma, Y., Sekihara, H., Kimura, S., Kadowaki, T. Diabetologia (2001) [Pubmed]
  24. Cyclooxygenase-2 expression in human colorectal cancer is unrelated to overall patient survival. Fux, R., Schwab, M., Thon, K.P., Gleiter, C.H., Fritz, P. Clin. Cancer Res. (2005) [Pubmed]
  25. Aspirin inhibits serine phosphorylation of insulin receptor substrate 1 in tumor necrosis factor-treated cells through targeting multiple serine kinases. Gao, Z., Zuberi, A., Quon, M.J., Dong, Z., Ye, J. J. Biol. Chem. (2003) [Pubmed]
  26. Inhibitors of TLR-9 act on multiple cell subsets in mouse and man in vitro and prevent death in vivo from systemic inflammation. Duramad, O., Fearon, K.L., Chang, B., Chan, J.H., Gregorio, J., Coffman, R.L., Barrat, F.J. J. Immunol. (2005) [Pubmed]
  27. Structural and evolutionary division of phosphotyrosine binding (PTB) domains. Uhlik, M.T., Temple, B., Bencharit, S., Kimple, A.J., Siderovski, D.P., Johnson, G.L. J. Mol. Biol. (2005) [Pubmed]
  28. Ewing's sarcoma of soft tissues in childhood: a report from the Intergroup Rhabdomyosarcoma Study, 1972 to 1991. Raney, R.B., Asmar, L., Newton, W.A., Bagwell, C., Breneman, J.C., Crist, W., Gehan, E.A., Webber, B., Wharam, M., Wiener, E.S., Anderson, J.R., Maurer, H.M. J. Clin. Oncol. (1997) [Pubmed]
  29. Gab1 coupling to the HGF/Met receptor multifunctional docking site requires binding of Grb2 and correlates with the transforming potential. Bardelli, A., Longati, P., Gramaglia, D., Stella, M.C., Comoglio, P.M. Oncogene (1997) [Pubmed]
  30. Identifying Cloninger's temperament profiles as related to the early development of the metabolic cardiovascular syndrome in young men. Keltikangas-Järvinen, L., Ravaja, N., Viikari, J. Arterioscler. Thromb. Vasc. Biol. (1999) [Pubmed]
  31. Invasive reperfusion study. II. Multicentre European randomized trial of anistreplase vs streptokinase in acute myocardial infarction. Pacouret, G., Charbonnier, B., Curien, N.D., Monassier, J.P., Cribier, A., Materne, P., Brochier, M.L., Letac, R., Hanssen, M., Sacrez, A. Eur. Heart J. (1991) [Pubmed]
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