Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Marina Tiemi ShioEmail author
  • Martin Olivier
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_309


Historical Background

The Src homology region 2 (SH) domain-containing protein tyrosine phosphatase-1 (SHP-1) is a member of the large family of protein tyrosine phosphatase (PTP). SHP-1 was identified in hematopoietic cells and organs involved in immune responses such as the spleen, thymus, lymph node, and bone marrow. SHP-1 is also known as hematopoietic cell phosphatase (HCP) because of its expression in these cells. Herein the nomenclature SHP-1 will be used. Back to the beginning of the 1990s, the study of tyrosine kinases was very well advanced; however, knowledge about their natural counterpart the tyrosine phosphatases was still greatly unraveled. Early on, different research groups isolated and identified a protein that...

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  1. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Abu-Dayyeh I, Shio MT, Sato S, Akira S, Cousineau B, Olivier M. Leishmania-induced IRAK-1 inactivation is mediated by SHP-1 interacting with an evolutionarily conserved KTIM motif. PLoS Negl Trop Dis. 2008;2:e305.PubMedPubMedCentralCrossRefGoogle Scholar
  3. An H, Hou J, Zhou J, Zhao W, Xu H, Zheng Y, et al. Phosphatase SHP-1 promotes TLR- and RIG-I-activated production of type I interferon by inhibiting the kinase IRAK1. Nat Immunol. 2008;9:542–50.CrossRefPubMedGoogle Scholar
  4. Caron D, Savard PE, Doillon CJ, Olivier M, Shink E, Lussier JG, et al. Protein tyrosine phosphatase inhibition induces anti-tumor activity: evidence of Cdk2/p27 kip1 and Cdk2/SHP-1 complex formation in human ovarian cancer cells. Cancer Lett. 2008;262:265–75.CrossRefPubMedGoogle Scholar
  5. Christophi GP, Panos M, Hudson CA, Christophi RL, Gruber RC, Mersich AT, et al. Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhanced inflammatory phenotype. Lab Investig. 2009;89:742–59.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Das S, Pandey K, Kumar A, Sardar AH, Purkait B, Kumar M, et al. TGF-beta1 re-programs TLR4 signaling in L. donovani infection: enhancement of SHP-1 and ubiquitin-editing enzyme A20. Immunol Cell Biol. 2012;90:640–54.CrossRefPubMedGoogle Scholar
  7. Dubois MJ, Bergeron S, Kim HJ, Dombrowski L, Perreault M, Fournes B, et al. The SHP-1 protein tyrosine phosphatase negatively modulates glucose homeostasis. Nat Med. 2006;12:549–56.CrossRefPubMedGoogle Scholar
  8. Geraldes P, Hiraoka-Yamamoto J, Matsumoto M, Clermont A, Leitges M, Marette A, et al. Activation of PKC-delta and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy. Nat Med. 2009;15:1298–306.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Gomez MA, Contreras I, Halle M, Tremblay ML, McMaster RW, Olivier M. Leishmania GP63 alters host signaling through cleavage-activated protein tyrosine phosphatases. Sci Signal. 2009;2:ra58.CrossRefPubMedGoogle Scholar
  10. Gomez MA, Alisaraie L, Shio MT, Berghuis AM, Lebrun C, Gautier-Luneau I, et al. Protein tyrosine phosphatases are regulated by mononuclear iron dicitrate. J Biol Chem. 2010;285:24620–8.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Green MC, Shultz LD. Motheaten, an immunodeficient mutant of the mouse. I Genet Pathol J Hered. 1975;66:250–8.Google Scholar
  12. Hassani K, Antoniak E, Jardim A, Olivier M. Temperature-induced protein secretion by Leishmania mexicana modulates macrophage signalling and function. PLoS One. 2011;6:e18724.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Kim EJ, Lee SM, Suk K, Lee WH. CD300a and CD300f differentially regulate the MyD88 and TRIF-mediated TLR signalling pathways through activation of SHP-1 and/or SHP-2 in human monocytic cell lines. Immunology. 2012;135:226–35.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 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.CrossRefPubMedGoogle Scholar
  16. Lorenz U. SHP-1 and SHP-2 in T cells: two phosphatases functioning at many levels. Immunol Rev. 2009;228:342–59.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Luo W, Mayeux J, Gutierrez T, Russell L, Getahun A, Muller J, et al. A balance between B cell receptor and inhibitory receptor signaling controls plasma cell differentiation by maintaining optimal Ets1 levels. J Immunol. 2014;193:909–20.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Mansfield JM, Olivier M. Immune evasion by parasites. Washington, DC: ASM Press; 2001.Google Scholar
  19. Martinez RJ, Morris AB, Neeld DK, Evavold BD. Targeted loss of SHP1 in murine thymocytes dampens TCR signaling late in selection. Eur J Immunol. 2016;46(9):2103–10.  https://doi.org/10.1002/eji..201646475.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Nandan D, Knutson KL, Lo R, Reiner NE. Exploitation of host cell signaling machinery: activation of macrophage phosphotyrosine phosphatases as a novel mechanism of molecular microbial pathogenesis. J Leukoc Biol. 2000;67:464–70.CrossRefPubMedGoogle Scholar
  21. Pao LI, Badour K, Siminovitch KA, Neel BG. Nonreceptor protein-tyrosine phosphatases in immune cell signaling. Annu Rev Immunol. 2007;25:473–523.CrossRefPubMedGoogle Scholar
  22. Poole AW, Jones ML. A SHPing tale: perspectives on the regulation of SHP-1 and SHP-2 tyrosine phosphatases by the C-terminal tail. Cell Signal. 2005;17:1323–32.CrossRefPubMedGoogle Scholar
  23. Rojas M, Olivier M, Garcia LF. Activation of JAK2/STAT1-alpha-dependent signaling events during Mycobacterium tuberculosis-induced macrophage apoptosis. Cell Immunol. 2002;217:58–66.CrossRefPubMedGoogle Scholar
  24. Roy S, Mandal C. Leishmania donovani utilize sialic acids for binding and phagocytosis in the macrophages through selective utilization of Siglecs and impair the innate immune arm. PLoS Negl Trop Dis. 2016;10:e0004904.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Sharma Y, Ahmad A, Bashir S, Elahi A, Khan F. Implication of protein tyrosine phosphatase SHP-1 in cancer-related signaling pathways. Future Oncol. 2016;12:1287–98.CrossRefPubMedGoogle Scholar
  26. Sooman L, Ekman S, Tsakonas G, Jaiswal A, Navani S, Edqvist PH, et al. PTPN6 expression is epigenetically regulated and influences survival and response to chemotherapy in high-grade gliomas. Tumour Biol. 2014;35:4479–88.CrossRefPubMedGoogle Scholar
  27. Stanford SM, Rapini N, Bottini N. Regulation of TCR signalling by tyrosine phosphatases: from immune homeostasis to autoimmunity. Immunology. 2012;137:1–19.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Tsubata T. Role of inhibitory BCR co-receptors in immunity. Infect Disord Drug Targets. 2012;12:181–90.CrossRefPubMedGoogle Scholar
  29. Tsui FW, Martin A, Wang J, Tsui HW. Investigations into the regulation and function of the SH2 domain-containing protein-tyrosine phosphatase, SHP-1. Immunol Res. 2006;35:127–36.CrossRefPubMedGoogle Scholar
  30. Van Avondt K, van Sorge NM, Meyaard L. Bacterial immune evasion through manipulation of host inhibitory immune signaling. PLoS Pathog. 2015;11:e1004644.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Watson HA, Wehenkel S, Matthews J, Ager A. SHP-1: the next checkpoint target for cancer immunotherapy? Biochem Soc Trans. 2016;44:356–62.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Wu C, Sun M, Liu L, Zhou GW. The function of the protein tyrosine phosphatase SHP-1 in cancer. Gene. 2003;306:1–12.CrossRefPubMedGoogle Scholar
  33. Xu E, Schwab M, Marette A. Role of protein tyrosine phosphatases in the modulation of insulin signaling and their implication in the pathogenesis of obesity-linked insulin resistance. Rev Endocr Metab Disord. 2014;15:79–97.  https://doi.org/10.1007/s11154-013-9282-4.CrossRefPubMedGoogle Scholar
  34. Zhou X, Wang H, Koles NL, Zhang A, Aronson NE. Leishmania infantum-chagasi activates SHP-1 and reduces NFAT5/TonEBP activity in the mouse kidney inner medulla. Am J Physiol Renal Physiol. 2014;307:F516–24.CrossRefPubMedGoogle Scholar
  35. Zhu Z, Oh SY, Cho YS, Zhang L, Kim YK, Zheng T. Tyrosine phosphatase SHP-1 in allergic and anaphylactic inflammation. Immunol Res. 2010;47:3–13.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Health Science programUniversidade Santo Amaro, programa de Ciência da SaúdeSão PauloBrazil
  2. 2.Infectious Diseases and Immunity in Global Health (IDIGH) ProgramResearch Institute of McGill University Health CentreMontrealCanada