Skip to main content

Advertisement

SpringerLink
Log in

Protein tyrosine phosphatase SHP-1: resurgence as new drug target for human autoimmune disorders

  • Review
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Recognition of self-antigen and its destruction by the immune system is the hallmark of autoimmune diseases. During the developmental stages, immune cells are introduced to the self-antigen, for which tolerance develops. The inflammatory insults that break the immune tolerance provoke immune system against self-antigen, progressively leading to autoimmune diseases. SH2 domain containing protein tyrosine phosphatase (PTP), SHP-1, was identified as hematopoietic cell-specific PTP that regulates immune function from developing immune tolerance to mediating cell signaling post-immunoreceptor activation. The extensive research on SHP-1-deficient mice elucidated the diversified role of SHP-1 in immune regulation, and inflammatory process and related disorders such as cancer, autoimmunity, and neurodegenerative diseases. The present review focalizes upon the implication of SHP-1 in the pathogenesis of autoimmune disorders, such as allergic asthma, neutrophilic dermatosis, atopic dermatitis, rheumatoid arthritis, and multiple sclerosis, so as to lay the background in pursuance of developing therapeutic strategies targeting SHP-1. Also, new SHP-1 molecular targets have been suggested like SIRP-α, PIPKIγ, and RIP-1 that may prove to be the focal point for the development of therapeutic strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. He R, Yu Z, Zhang R, Zhang Z. Protein tyrosine phosphatases as potential therapeutic targets. Acta Pharmacol Sin. 2014;35:1227–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Alonso A, Sasin J, Bottini N, et al. Protein tyrosine phosphatases in the human genome. Cell. 2004;117:699–711.

    Article  CAS  PubMed  Google Scholar 

  3. Xu K, Li S, Yang W, et al. Structural and biochemical analysis of tyrosine phosphatase related to biofilm formation A (TpbA) from the opportunistic pathogen Pseudomonas aeruginosa PAO1. PLoS One. 2015;10(4):e0124330.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Johnson KG, Van VD. Receptor protein tyrosine phosphatases in nervous system development. Physiol Rev. 2003;83:1–24.

    Article  CAS  PubMed  Google Scholar 

  5. Marín-Juez R, Jong-Raadsen S, Yang S, Spaink HP. Hyperinsulinemia induces insulin resistance and immune suppression via Ptpn6/Shp1 in zebrafish. J Endocrinol. 2014;222:229–41.

    Article  PubMed  Google Scholar 

  6. Mannell H, Krotz F. SHP-2 regulates growth factor dependent vascular signalling and function. Mini Rev Med Chem. 2014;14:471–83.

    Article  CAS  PubMed  Google Scholar 

  7. Kozicky LK, Sly LM. Phosphatase regulation of macrophage activation. Semin Immunol. 2015;27:276–85.

    Article  CAS  PubMed  Google Scholar 

  8. Abram CL, Roberge GL, Pao LI, Neel BG, Lowell CA. Distinct roles for neutrophils and dendritic cells in inflammation and autoimmunity in motheaten mice. Immunity. 2013;38:489–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Green MC, Shultz LD. Motheaten, an immunodeficient mutant of the mouse. I. Genet Pathol J Hered. 1975;66:250–8.

    CAS  Google Scholar 

  10. Bignon JS, Siminovitch KA. Identification of PTP1C mutation as the genetic defect in motheaten and viable motheaten mice: a step toward defining the roles of protein tyrosine phosphatases in the regulation of hemopoietic cell differentiation and function. Clin Immunol Immunopathol. 1994;73:168–79.

    Article  CAS  PubMed  Google Scholar 

  11. Tsui HW, Siminovitch KA, de Souza L, Tsui FW. Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase gene. Nat Genet. 1993;4:124–9.

    Article  CAS  PubMed  Google Scholar 

  12. Kozlowski M, Mlinaric-Rascan I, Feng GS, Shen R, Pawson T, Siminovitch KA. Expression and catalytic activity of the tyrosine phosphatase PTP1C is severely impaired in motheaten and viable motheaten mice. J Exp Med. 1993;178:2157–63.

    Article  CAS  PubMed  Google Scholar 

  13. Sidman CL, Marshall JD, Allen RD. Murine “viable motheaten” mutation reveals a gene critical to the development of both B and T lymphocytes. Proc Natl Acad Sci USA. 1989;86:6279–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hayes SM, Shultz LD, Greiner DL. Thymic involution in viable motheaten (me(v)) mice is associated with a loss of intrathymic precursor activity. Dev Immunol. 1992;2:191–205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Christianson SW, Greiner DL, Deluca D, et al. T cell developmental defects in ‘viable motheaten’ mice deficient in SHP-1 protein-tyrosine phosphatase. Developmental defects are corrected in vitro in the presence of normal hematopoietic-origin stromal cells and in vivo by exogenous IL-7. J Autoimmun. 2002;18:119–30.

    Article  PubMed  Google Scholar 

  16. Nakayama K, Takahashi K, Shultz LD, Miyakawa K, Tomita K. Abnormal development and differentiation of macrophages and dendritic cells in viable motheaten mutant mice deficient in haematopoietic cell phosphatase. Int J Exp Pathol. 1997;78:245–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Thrall RS, Vogel SN, Evans R, Shultz LD. Role of tumor necrosis factor-alpha in the spontaneous development of pulmonary fibrosis in viable motheaten mutant mice. Am J Pathol. 1997;151:1303–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Kruger J, Butler JR, Cherapanov V, et al. Deficiency of Src homology 2-containing phosphatase 1 results in abnormalities in murine neutrophil function: studies in motheaten mice. J Immunol. 2000;165:5847–59.

    Article  CAS  PubMed  Google Scholar 

  19. Aoki K, Didomenico E, Sims NA, et al. The tyrosine phosphatase SHP-1 is a negative regulator of osteoclastogenesis and osteoclast resorbing activity: increased resorption and osteopenia in me(v)/me(v) mutant mice. Bone. 1999;25:261–7.

    Article  CAS  PubMed  Google Scholar 

  20. Lyons BL, Lynes MA, Burzenski L, Joliat MJ, Hadjout N, Shultz LD. Mechanisms of anemia in SHP-1 protein tyrosine phosphatase-deficient “viable motheaten” mice. Exp Hematol. 2003;31:234–43.

    Article  CAS  PubMed  Google Scholar 

  21. Malissen B, Grégoire C, Malissen M, Roncagalli R. Integrative biology of T cell activation. Nat Immunol. 2014;15:790–7.

    Article  CAS  PubMed  Google Scholar 

  22. Love PE, Hayes SM. ITAM-mediated signaling by the T-Cell antigen receptor. Cold Spring Harb Perspect Biol. 2010;2:a002485.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lorenz U. SHP-1 and SHP-2 in T cells: two phosphatases functioning at many levels. Immunol Rev. 2009;228:342–59.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Fu G, Rybakin V, Brzostek J, Paster W, Acuto O, Gascoigne NR. Fine-tuning T cell receptor signaling to control T cell development. Trends Immunol. 2014;35:311–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Fu G, Casas J, Rigaud S. Themis sets the signal threshold for positive and negative selection in T-cell development. Nature. 2013;504:441–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Park HS, do Jun Y, Han CR, Woo HJ, Kim YH. Proteasome inhibitor MG132-induced apoptosis via ER stress-mediated apoptotic pathway and its potentiation by protein tyrosine kinase p56lck in human Jurkat T cells. Biochem Pharmacol. 2011;82:1110–25.

    Article  CAS  PubMed  Google Scholar 

  27. Robles-Escajeda E, Lerma D, Nyakeriga AM, Ross JA, Kirken RA, Aguilera RJ, Varela-Ramirez A. Searching in mother nature for anti-cancer activity: anti-proliferative and pro-apoptotic effect elicited by green barley on leukemia/lymphoma cells. PLoS One. 2013;8:e73508.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Johnson DJ, Pao LI, Dhanji S, Murakami K, Ohashi PS, Neel BG. Shp1 regulates T cell homeostasis by limiting IL-4 signals. J Exp Med. 2013;210:1419–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Iype T, Sankarshanan M, Mauldin IS, Mullins DW, Lorenz U. The protein tyrosine phosphatase SHP-1 modulates the suppressive activity of regulatory T cells. J Immunol. 2010;185:6115–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Yu WM, Wang S, Keegan AD, Williams MS, Qu CK. Abnormal Th1 cell differentiation and IFN-gamma production in T lymphocytes from motheaten viable mice mutant for Src homology 2 domain-containing protein tyrosine phosphatase-1. J Immunol. 2005;174:1013–9.

    Article  CAS  PubMed  Google Scholar 

  31. Park IK, Shultz LD, Letterio JJ, Gorham JD. TGF-beta1 inhibits T-bet induction by IFN-gamma in murine CD4+ T cells through the protein tyrosine phosphatase Src homology region 2 domain containing phosphatase-1. J Immunol. 2005;175:5666–74.

    Article  CAS  PubMed  Google Scholar 

  32. Stanford SM, Rapini N, Bottini N. Regulation of TCR signalling by tyrosine phosphatases: from immune homeostasis to autoimmunity. Immunology. 2012;137:1–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sankarshanan M, Ma Z, Iype T, Lorenz U. Identification of a novel lipid raft-targeting motif in Src homology 2-containing phosphatase 1. J Immunol. 2007;179:483–90.

    Article  CAS  PubMed  Google Scholar 

  34. Zhang L, Oh SY, Wu X, et al. SHP-1 deficient mast cells are hyperresponsive to stimulation and critical in initiating allergic inflammation in the lung. J Immunol. 2010;184:1180–90.

    Article  CAS  PubMed  Google Scholar 

  35. Dwivedi G, Gran MA, Bagchi P, Kemp ML. Dynamic redox regulation of IL-4 signaling. PLoS Comput Biol. 2015;11(11):e1004582.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Li X, Kwon O, Kim DY, Taketomi Y, Murakami M, Chang HW. NecroX-5 suppresses IgE/Ag-stimulated anaphylaxis and mast cell activation by regulating the SHP-1-Syk signaling module. Allergy. 2016;71:198–209.

    Article  CAS  PubMed  Google Scholar 

  37. Frijhoff J, Dagnell M, Godfrey R, Ostman A. Regulation of protein tyrosine phosphatase oxidation in cell adhesion and migration. Antioxid Redox Signal. 2014;20:1994–2010.

    Article  CAS  PubMed  Google Scholar 

  38. Zhou L, Oh SY, Zhou Y, et al. SHP-1 regulation of mast cell function in allergic inflammation and anaphylaxis. PLoS One. 2013;8:e55763.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wang Y, Zhu Z, Church TD, et al. SHP-1 as a critical regulator of Mycoplasma pneumoniae-induced inflammation in human asthmatic airway epithelial cells. J Immunol. 2012;188:3371–81.

    Article  CAS  PubMed  Google Scholar 

  40. Cho SH, Oh SY, Lane AP, et al. Regulation of nasal airway homeostasis and inflammation in mice by SHP-1 and Th2/Th1 signaling pathways. PLoS One. 2014;4(9):e103685.

    Article  Google Scholar 

  41. Ando T, Xiao W, Gao P, et al. Critical role for mast cell Stat5 activity in skin inflammation. Cell Rep. 2014;6:366–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Xu X, Jin T. The novel functions of the PLC/PKC/PKD signaling axis in g protein-coupled receptor-mediated chemotaxis of neutrophils. J Immunol Res. 2015;2015:817604.

    PubMed  PubMed Central  Google Scholar 

  43. Hsiao WY, Lin YC, Liao FH, Chan YC, Huang CY. Dual-specificity phosphatase 4 regulates STAT5 protein stability and helper T cell polarization. PLoS ONE. 2015;10:e0145880.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Alavi A, Sajic D, Cerci FB, Ghazarian D, Rosenbach M, Jorizzo J. Neutrophilic dermatoses: an update. Am J Clin Dermatol. 2014;15:413–23.

    Article  PubMed  Google Scholar 

  45. Demosthenous C, Han JJ, Hu G, Stenson M, Gupta M. Loss of function mutations in PTPN6 promote STAT3 deregulation via JAK3 kinase in diffuse large B-cell lymphoma. Oncotarget. 2015;6:44703–13.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Caignard G, Eva MM, van Bruggen R, et al. Mouse ENU mutagenesis to understand immunity to infection: methods, selected examples, and perspectives. Genes. 2014;5:887–925.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Lukens JR, Kanneganti TD. SHP-1 and IL-1α conspire to provoke neutrophilic dermatoses. Rare Dis. 2014;31(2):e27742.

    Article  Google Scholar 

  48. Lukens JR, Vogel P, Johnson GR, et al. RIP1-driven autoinflammation targets IL-1α independently of inflammasomes and RIP3. Nature. 2013;498:224–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Chen CJ, Kono H, Golenbock D, Reed G, Akira S, Rock KL. Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nat Med. 2007;13:851–6.

    Article  CAS  PubMed  Google Scholar 

  50. Cohen I, Rider P, Carmi Y, et al. Differential release of chromatin-bound IL-1alpha discriminates between necrotic and apoptotic cell death by the ability to induce sterile inflammation. Proc Natl Acad Sci USA. 2010;107:2574–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Stadtmann A, Block H, Volmering S, et al. Cross-talk between Shp1 and PIPKIγ controls leukocyte recruitment. J Immunol. 2015;195:1152–61.

    Article  CAS  PubMed  Google Scholar 

  52. Xu Q, Zhang Y, Xiong X, et al. PIPKIγ targets to the centrosome and restrains centriole duplication. J Cell Sci. 2014;127:1293–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Mkaddem SB, Hayem G, Jönsson F, et al. Shifting FcγRIIA-ITAM from activation to inhibitory configuration ameliorates arthritis. J Clin Invest. 2014;124:3945–59.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Li J, Yang P, Wu Q, et al. Death receptor 5-targeted depletion of interleukin-23-producing macrophages, Th17, and Th1/17 associated with defective tyrosine phosphatase in mice and patients with rheumatoid arthritis. Arthritis Rheum. 2013;65:2594–605.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Eriksen KW, Woetmann A, Skov L, et al. Deficient SOCS3 and SHP-1 expression in psoriatic T cells. J Invest Dermatol. 2010;130:1590–7.

    Article  CAS  PubMed  Google Scholar 

  56. Chandra A, Ray A, Senapati S, Chatterjee R. Genetic and epigenetic basis of psoriasis pathogenesis. Mol Immunol. 2015;64:313–23.

    Article  CAS  PubMed  Google Scholar 

  57. Blank T, Prinz M. NF-κB signaling regulates myelination in the CNS. Front Mol Neurosci. 2014;7:47.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Kim JH, Choi DJ, Jeong HK, et al. DJ-1 facilitates the interaction between STAT1 and its phosphatase, SHP-1, in brain microglia and astrocytes: a novel anti-inflammatory function of DJ-1. Neurobiol Dis. 2013;60:1–10.

    Article  CAS  PubMed  Google Scholar 

  59. Hernández-Pedro NY, Espinosa-Ramirez G, de la Cruz VP, Pineda B, Sotelo J. Initial immunopathogenesis of multiple sclerosis: innate immune response. Clin Dev Immunol. 2013;2013:413465.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Mallucci G, Peruzzotti-Jametti L, Bernstock JD, Pluchino S. The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis. Prog Neurobiol. 2015;127–128:1–22.

    Article  PubMed  Google Scholar 

  61. Kumagai C, Kalman B, Middleton FA, Vyshkina T, Massa PT. Increased promoter methylation of the immune regulatory gene SHP-1 in leukocytes of multiple sclerosis subjects. J Neuroimmunol. 2012;246:51–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Christophi GP, Gruber RC, Panos M, Christophi RL, Jubelt B, Massa PT. Interleukin-33 upregulation in peripheral leukocytes and CNS of multiple sclerosis patients. Clin Immunol. 2012;142:308–19.

    Article  CAS  PubMed  Google Scholar 

  63. Christophi GP, Panos M, Hudson CA, et al. Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhanced inflammatory phenotype. Lab Invest. 2009;89:742–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Christophi GP, Hudson CA, Gruber RC, et al. SHP-1 deficiency and increased inflammatory gene expression in PBMCs of multiple sclerosis patients. Lab Invest. 2008;88:243–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Pesce M, Ferrone A, Rizzuto A, et al. The SHP-1 expression is associated with cytokines and psychopathological status in unmedicated first episode schizophrenia patients. Brain Behav Immun. 2014;41:251–60.

    Article  CAS  PubMed  Google Scholar 

  66. Gruber RC, LaRocca D, Minchenberg SB, et al. The control of reactive oxygen species production by SHP-1 in oligodendrocytes. Glia. 2015;63:1753–71.

    Article  PubMed  Google Scholar 

  67. Sauer EL, Cloake NC, Greer JM. Taming the TCR: antigen-specific immunotherapeutic agents for autoimmune diseases. Int Rev Immunol. 2015;34:460–85.

    Article  CAS  PubMed  Google Scholar 

  68. Murata Y, Saito Y, Kaneko T, et al. Autoimmune animal models in the analysis of the CD47–SIRPα signaling pathway. Methods. 2014;65:254–9.

    Article  CAS  PubMed  Google Scholar 

  69. Watson NB, Schneider KM, Massa PT. SHP-1-dependent macrophage differentiation exacerbates virus-induced myositis. J Immunol. 2015;194:2796–809.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Son KN, Lipton HL. Inhibition of Theiler’s virus-induced apoptosis in infected murine macrophages results in necroptosis. Virus Res. 2015;195:177–82.

    Article  CAS  PubMed  Google Scholar 

  71. Heneberg P. Reactive nitrogen species and hydrogen sulfide as regulators of protein tyrosine phosphatase activity. Antioxid Redox Signal. 2014;20:2191–209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Zhao J, Lurie DI. Cochlear ablation in mice lacking SHP-1 results in an extended period of cell death of anteroventral cochlear nucleus neurons. Hear Res. 2004;189:63–75.

    Article  PubMed  Google Scholar 

  73. Kaminska B, Mota M, Pizzi M. Signal transduction and epigenetic mechanisms in the control of microglia activation during neuroinflammation. Biochim Biophys Acta. 2016;1862:339–51.

    Article  CAS  PubMed  Google Scholar 

  74. Alig SK, Stampnik Y, Pircher J, et al. The tyrosine phosphatase SHP-1 regulates hypoxia inducible factor-1α (HIF-1α) protein levels in endothelial cells under hypoxia. PLoS One. 2015;10(3):e0121113.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Deng C, Wu B, Yang H, et al. Decreased expression of Src homology 2 domain-containing protein tyrosine phosphatase 1 reduces T cell activation threshold but not the severity of experimental autoimmune myasthenia gravis. J Neuroimmunol. 2003;138:76–82.

    Article  CAS  PubMed  Google Scholar 

  76. Youinou P, Renaudineau Y. CD5 expression in B cells from patients with systemic lupus erythematosus. Crit Rev Immunol. 2011;31:31–42.

    Article  CAS  PubMed  Google Scholar 

  77. Kundu S, Fan K, Cao M, et al. Novel SHP-1 inhibitors tyrosine phosphatase inhibitor-1 and analogs with preclinical anti-tumor activities as tolerated oral agents. J Immunol. 2010;184:6529–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Lu L, Wang S, Zhu M, et al. Inhibition protein tyrosine phosphatases by an oxovanadium glutamate complex, Na2[VO(Glu)2(CH3OH)](Glu = glutamate). Biometals. 2010;23:1139–47.

    Article  CAS  PubMed  Google Scholar 

  79. Yi T, Elson P, Mitsuhashi M, et al. Phosphatase inhibitor, sodium stibogluconate, in combination with interferon (IFN) alpha 2b: phase I trials to identify pharmacodynamic and clinical effects. Oncotarget. 2011;2:1155–64.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Yang JW, He XP, Li C, et al. A unique and rapid approach toward the efficient development of novel protein tyrosine phosphatase (PTP) inhibitors based on ‘clicked’ pseudo-glycopeptides. Bioorg Med Chem Lett. 2011;21:1092–6.

    Article  CAS  PubMed  Google Scholar 

  81. Li Y, Lu L, Zhu M, et al. Potent inhibition of protein tyrosine phosphatases by copper complexes with multi-benzimidazole derivatives. Biometals. 2011;24:993–1004.

    Article  CAS  PubMed  Google Scholar 

  82. Wang Q, Zhu M, Lu L, Yuan C, Xing S, Fu X. Potent inhibition of protein tyrosine phosphatases by quinquedentate binuclear copper complexes: synthesis, characterization and biological activities. Dalton Trans. 2011;40:12926–34.

    Article  CAS  PubMed  Google Scholar 

  83. Lu L, Gao X, Zhu M, et al. Exploration of biguanido–oxovanadium complexes as potent and selective inhibitors of protein tyrosine phosphatases. Biometals. 2012;25:599–610.

    Article  CAS  PubMed  Google Scholar 

  84. Akiba H, Sumaoka J, Hamakubo T, Komiyama M. Conjugation-free, visual, and quantitative evaluation of inhibitors on protein tyrosine kinases and phosphatases with a luminescent Tb(III) complex. Anal Bioanal Chem. 2014;406:2957–64.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

YS acknowledge University Grant Commission (UGC) for awarding senior research fellowship (SRF). FK thank Indian Council of Medical Research (ICMR) for funding support.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Faculty of Science, Jamia Hamdard, New Delhi, 110062, India

    Yadhu Sharma, Samina Bashir, Puja Bhardwaj & Farah Khan

  2. Department of Botany, Aligarh Muslim University, Aligarh, Uttar Pradesh, 202002, India

    Altaf Ahmad

Authors
  1. Yadhu Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Samina Bashir
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Puja Bhardwaj
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Altaf Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Farah Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Farah Khan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sharma, Y., Bashir, S., Bhardwaj, P. et al. Protein tyrosine phosphatase SHP-1: resurgence as new drug target for human autoimmune disorders. Immunol Res 64, 804–819 (2016). https://doi.org/10.1007/s12026-016-8805-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-016-8805-y

Keywords

Search

Navigation