PTPN6

PTPN6

PTPN6

Protein-coding gene in humans


Tyrosine-protein phosphatase non-receptor type 6, also known as Src homology region 2 domain-containing phosphatase-1 (SHP-1), is an enzyme that in humans is encoded by the PTPN6 gene.[5]

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Function

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. N-terminal part of this PTP contains two tandem Src homolog (SH2) domains, which act as protein phospho-tyrosine binding domains, and mediate the interaction of this PTP with its substrates. This PTP is expressed primarily in hematopoietic cells, and functions as an important regulator of multiple signaling pathways in hematopoietic cells. This PTP has been shown to interact with, and dephosphorylate a wide spectrum of phospho-proteins involved in hematopoietic cell signaling, (e.g., the LYN-CD22-SHP-1 pathway). Multiple alternatively spliced variants of this gene, which encode distinct isoforms, have been reported.[6]

Expression

SHP-1 gene has two promoters: P-1, active in epithelial cells, and P-2, active in hemopoietic cells. In addition the expression of SHP-1 is low in epithelial cells and high in hemopoietic cells. SHP-1 level in epithelial cells increases and in hematopoietic cells decreases in cancer.[7]

Interactions

PTPN6 has been shown to interact with:


References

  1. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  2. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. Plutzky J, Neel BG, Rosenberg RD, Eddy RL, Byers MG, Jani-Sait S, Shows TB (August 1992). "Chromosomal localization of an SH2-containing tyrosine phosphatase (PTPN6)". Genomics. 13 (3): 869–72. doi:10.1016/0888-7543(92)90172-O. PMID 1639416.
  4. Amin S, Kumar A, Nilchi L, Wright K, Kozlowski M (August 2011). "Breast cancer cells proliferation is regulated by tyrosine phosphatase SHP1 through c-jun N-terminal kinase and cooperative induction of RFX-1 and AP-4 transcription factors". Mol. Cancer Res. 9 (8): 1112–25. doi:10.1158/1541-7786.MCR-11-0097. PMID 21719561. S2CID 33833067.
  5. Liedtke M, Pandey P, Kumar S, Kharbanda S, Kufe D (October 1998). "Regulation of Bcr-Abl-induced SAP kinase activity and transformation by the SHPTP1 protein tyrosine phosphatase". Oncogene. 17 (15): 1889–92. doi:10.1038/sj.onc.1202117. PMID 9788431. S2CID 42228230.
  6. Kozlowski M, Larose L, Lee F, Le DM, Rottapel R, Siminovitch KA (April 1998). "SHP-1 binds and negatively modulates the c-Kit receptor by interaction with tyrosine 569 in the c-Kit juxtamembrane domain". Mol. Cell. Biol. 18 (4): 2089–99. doi:10.1128/mcb.18.4.2089. PMC 121439. PMID 9528781.
  7. Law CL, Sidorenko SP, Chandran KA, Zhao Z, Shen SH, Fischer EH, Clark EA (February 1996). "CD22 associates with protein tyrosine phosphatase 1C, Syk, and phospholipase C-gamma(1) upon B cell activation". J. Exp. Med. 183 (2): 547–60. doi:10.1084/jem.183.2.547. PMC 2192439. PMID 8627166.
  8. Adachi T, Wienands J, Wakabayashi C, Yakura H, Reth M, Tsubata T (July 2001). "SHP-1 requires inhibitory co-receptors to down-modulate B cell antigen receptor-mediated phosphorylation of cellular substrates". J. Biol. Chem. 276 (28): 26648–55. doi:10.1074/jbc.M100997200. PMID 11356834.
  9. Pumphrey NJ, Taylor V, Freeman S, Douglas MR, Bradfield PF, Young SP, Lord JM, Wakelam MJ, Bird IN, Salmon M, Buckley CD (April 1999). "Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31". FEBS Lett. 450 (1–2): 77–83. doi:10.1016/s0014-5793(99)00446-9. PMID 10350061. S2CID 31471121.
  10. Keilhack H, Hellman U, van Hengel J, van Roy F, Godovac-Zimmermann J, Böhmer FD (August 2000). "The protein-tyrosine phosphatase SHP-1 binds to and dephosphorylates p120 catenin". J. Biol. Chem. 275 (34): 26376–84. doi:10.1074/jbc.M001315200. PMID 10835420.
  11. Keilhack H, Tenev T, Nyakatura E, Godovac-Zimmermann J, Nielsen L, Seedorf K, Böhmer FD (September 1998). "Phosphotyrosine 1173 mediates binding of the protein-tyrosine phosphatase SHP-1 to the epidermal growth factor receptor and attenuation of receptor signaling". J. Biol. Chem. 273 (38): 24839–46. doi:10.1074/jbc.273.38.24839. PMID 9733788.
  12. Xu MJ, Zhao R, Cao H, Zhao ZJ (May 2002). "SPAP2, an Ig family receptor containing both ITIMs and ITAMs". Biochem. Biophys. Res. Commun. 293 (3): 1037–46. doi:10.1016/S0006-291X(02)00332-7. PMID 12051764.
  13. Ganju RK, Brubaker SA, Chernock RD, Avraham S, Groopman JE (June 2000). "Beta-chemokine receptor CCR5 signals through SHP1, SHP2, and Syk". J. Biol. Chem. 275 (23): 17263–8. doi:10.1074/jbc.M000689200. PMID 10747947.
  14. Kon-Kozlowski M, Pani G, Pawson T, Siminovitch KA (February 1996). "The tyrosine phosphatase PTP1C associates with Vav, Grb2, and mSos1 in hematopoietic cells". J. Biol. Chem. 271 (7): 3856–62. doi:10.1074/jbc.271.7.3856. PMID 8632004.
  15. Jiao H, Berrada K, Yang W, Tabrizi M, Platanias LC, Yi T (December 1996). "Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1". Mol. Cell. Biol. 16 (12): 6985–92. doi:10.1128/mcb.16.12.6985. PMC 231702. PMID 8943354.
  16. Wu DW, Stark KC, Dunnington D, Dillon SB, Yi T, Jones C, Pelus LM (February 2000). "SH2-Containing protein tyrosine phosphatase-1 (SHP-1) association with Jak2 in UT-7/Epo cells". Blood Cells Mol. Dis. 26 (1): 15–24. doi:10.1006/bcmd.2000.0273. PMID 10772872.
  17. Sathish JG, Johnson KG, Fuller KJ, LeRoy FG, Meyaard L, Sims MJ, Matthews RJ (February 2001). "Constitutive association of SHP-1 with leukocyte-associated Ig-like receptor-1 in human T cells". J. Immunol. 166 (3): 1763–70. doi:10.4049/jimmunol.166.3.1763. PMID 11160222.
  18. Fournier N, Chalus L, Durand I, Garcia E, Pin JJ, Churakova T, Patel S, Zlot C, Gorman D, Zurawski S, Abrams J, Bates EE, Garrone P (August 2000). "FDF03, a novel inhibitory receptor of the immunoglobulin superfamily, is expressed by human dendritic and myeloid cells". J. Immunol. 165 (3): 1197–209. doi:10.4049/jimmunol.165.3.1197. PMID 10903717.
  19. Meyaard L, Adema GJ, Chang C, Woollatt E, Sutherland GR, Lanier LL, Phillips JH (August 1997). "LAIR-1, a novel inhibitory receptor expressed on human mononuclear leukocytes". Immunity. 7 (2): 283–90. doi:10.1016/s1074-7613(00)80530-0. hdl:2066/26173. PMID 9285412.
  20. Fanger NA, Cosman D, Peterson L, Braddy SC, Maliszewski CR, Borges L (November 1998). "The MHC class I binding proteins LIR-1 and LIR-2 inhibit Fc receptor-mediated signaling in monocytes". Eur. J. Immunol. 28 (11): 3423–34. doi:10.1002/(SICI)1521-4141(199811)28:11<3423::AID-IMMU3423>3.0.CO;2-2. PMID 9842885.
  21. Colonna M, Samaridis J, Cella M, Angman L, Allen RL, O'Callaghan CA, Dunbar R, Ogg GS, Cerundolo V, Rolink A (April 1998). "Human myelomonocytic cells express an inhibitory receptor for classical and nonclassical MHC class I molecules". J. Immunol. 160 (7): 3096–100. doi:10.4049/jimmunol.160.7.3096. PMID 9531263.
  22. Lorenz U, Ravichandran KS, Pei D, Walsh CT, Burakoff SJ, Neel BG (March 1994). "Lck-dependent tyrosyl phosphorylation of the phosphotyrosine phosphatase SH-PTP1 in murine T cells". Mol. Cell. Biol. 14 (3): 1824–34. doi:10.1128/mcb.14.3.1824. PMC 358540. PMID 8114715.
  23. Binstadt BA, Billadeau DD, Jevremović D, Williams BL, Fang N, Yi T, Koretzky GA, Abraham RT, Leibson PJ (October 1998). "SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors". J. Biol. Chem. 273 (42): 27518–23. doi:10.1074/jbc.273.42.27518. PMID 9765283.
  24. Yoshida K, Kufe D (December 2001). "Negative regulation of the SHPTP1 protein tyrosine phosphatase by protein kinase C delta in response to DNA damage". Mol. Pharmacol. 60 (6): 1431–8. doi:10.1124/mol.60.6.1431. PMID 11723252.
  25. Kumar S, Avraham S, Bharti A, Goyal J, Pandey P, Kharbanda S (October 1999). "Negative regulation of PYK2/related adhesion focal tyrosine kinase signal transduction by hematopoietic tyrosine phosphatase SHPTP1". J. Biol. Chem. 274 (43): 30657–63. doi:10.1074/jbc.274.43.30657. PMID 10521452.
  26. Keilhack H, Müller M, Böhmer SA, Frank C, Weidner KM, Birchmeier W, Ligensa T, Berndt A, Kosmehl H, Günther B, Müller T, Birchmeier C, Böhmer FD (January 2001). "Negative regulation of Ros receptor tyrosine kinase signaling. An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1". J. Cell Biol. 152 (2): 325–34. doi:10.1083/jcb.152.2.325. PMC 2199605. PMID 11266449.
  27. Yang J, Cheng Z, Niu T, Liang X, Zhao ZJ, Zhou GW (February 2000). "Structural basis for substrate specificity of protein-tyrosine phosphatase SHP-1". J. Biol. Chem. 275 (6): 4066–71. doi:10.1074/jbc.275.6.4066. PMID 10660565.
  28. Yetter A, Uddin S, Krolewski JJ, Jiao H, Yi T, Platanias LC (August 1995). "Association of the interferon-dependent tyrosine kinase Tyk-2 with the hematopoietic cell phosphatase". J. Biol. Chem. 270 (31): 18179–82. doi:10.1074/jbc.270.31.18179. PMID 7629131.

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