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Published in:

01-06-2008

The tyrosine phosphatase Shp2 (PTPN11) in cancer

Authors: Gordon Chan, Demetrios Kalaitzidis, Benjamin G. Neel

Published in: Cancer and Metastasis Reviews | Issue 2/2008

Abstract

Diverse cellular processes are regulated by tyrosyl phosphorylation, which is controlled by protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs). De-regulated tyrosyl phosphorylation, evoked by gain-of-function mutations and/or over-expression of PTKs, contributes to the pathogenesis of many cancers and other human diseases. PTPs, because they oppose the action of PTKs, had been considered to be prime suspects for potential tumor suppressor genes. Surprisingly, few, if any, tumor suppressor PTPs have been identified. However, the Src homology-2 domain-containing phosphatase Shp2 (encoded by PTPN11) is a bona fide proto-oncogene. Germline mutations in PTPN11 cause Noonan and LEOPARD syndromes, whereas somatic PTPN11 mutations occur in several types of hematologic malignancies, most notably juvenile myelomonocytic leukemia and, more rarely, in solid tumors. Shp2 also is an essential component in several other oncogene signaling pathways. Elucidation of the events underlying Shp2-evoked transformation may provide new insights into oncogenic mechanisms and novel targets for anti-cancer therapy.

Mohi, M. G., & Neel, B. G. (2007). The role of Shp2 (PTPN11) in cancer. Current Opinion in Genetics & Development, 17(1), 23–30.CrossRef

Neel, B. G., Gu, H., & Pao, L. (2003). The ‘Shp’ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends in Biochemical Sciences, 28(6), 284–293.PubMedCrossRef

Pao, L. I., Badour, K., Siminovitch, K. A., & Neel, B. G. (2007). Nonreceptor protein-tyrosine phosphatases in immune cell signaling. Annual Review of Immunology, 25, 473–523.PubMedCrossRef

Feng, G. S. (1999). Shp-2 tyrosine phosphatase: signaling one cell or many. Experimental Cell Research, 253(1), 47–54.PubMedCrossRef

Chan, R. J., & Feng, G. S. (2007). PTPN11 is the first identified proto-oncogene that encodes a tyrosine phosphatase. Blood, 109(3), 862–867.PubMedCrossRef

Tartaglia, M., Mehler, E. L., Goldberg, R., Zampino, G., Brunner, H. G., Kremer, H., et al. (2001). Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nature Genetics, 29(4), 465–468.PubMedCrossRef

Tartaglia, M., & Gelb, B. D. (2005). Noonan syndrome and related disorders: Genetics and pathogenesis. Annual Review of Genomics and Human Genetics, 6, 45–68.PubMedCrossRef

Tartaglia, M., Niemeyer, C. M., Shannon, K. M., & Loh, M. L. (2004). SHP-2 and myeloid malignancies. Current Opinion in Hematology, 11(1), 44–50.PubMedCrossRef

Tartaglia, M., Niemeyer, C. M., Fragale, A., Song, X., Buechner, J., Jung, A., et al. (2003). Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nature Genetics, 34(2), 148–150.PubMedCrossRef

10.

Loh, M. L., Vattikuti, S., Schubbert, S., Reynolds, M. G., Carlson, E., Lieuw, K. H., et al. (2004). Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis. Blood, 103(6), 2325–2331.PubMedCrossRef

11.

Neel, B., Gu, H., & Pao, L. (2003). SH2 domain-containing protein tyrosine phosphatases. In R. A. Bradshaw, & E. A. Dennis (Eds.) Handbook cell signaling pp. 707–730. Amsterdam: Elsevier.CrossRef

12.

Gelb, B. D., & Tartaglia, M. (2006). Noonan syndrome and related disorders: dysregulated RAS-mitogen activated protein kinase signal transduction. Human Molecular Genetics, 15(Spec No 2), R220–226.PubMedCrossRef

13.

Tonks, N. K., & Neel, B. G. (2001). Combinatorial control of the specificity of protein tyrosine phosphatases. Current Opinion in Cell Biology, 13(2), 182–195.PubMedCrossRef

14.

Van Vactor, D., O’Reilly, A. M., & Neel, B. G. (1998). Genetic analysis of protein tyrosine phosphatases. Current Opinion in Genetics & Development, 8(1), 112–126.CrossRef

15.

Araki, T., Nawa, H., & Neel, B. G. (2003). Tyrosyl phosphorylation of Shp2 is required for normal ERK activation in response to some, but not all, growth factors. Journal of Biological Chemistry, 278(43), 41677–41684.PubMedCrossRef

16.

Hof, P., Pluskey, S., Dhe-Paganon, S., Eck, M. J., & Shoelson, S. E. (1998). Crystal structure of the tyrosine phosphatase SHP-2. Cell, 92(4), 441–450.PubMedCrossRef

17.

Barford, D., & Neel, B. G. (1998). Revealing mechanisms for SH2 domain mediated regulation of the protein tyrosine phosphatase SHP-2. Structure, 6(3), 249–254.PubMedCrossRef

18.

O’Reilly, A. M., Pluskey, S., Shoelson, S. E., & Neel, B. G. (2000). Activated mutants of SHP-2 preferentially induce elongation of Xenopus animal caps. Molecular and Cellular Biology, 20(1), 299–311.PubMed

19.

Zhang, S. Q., Yang, W., Kontaridis, M. I., Bivona, T. G., Wen, G., Araki, T., et al. (2004). Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment. Molecular Cell, 13(3), 341–355.PubMedCrossRef

20.

Ren, Y., Meng, S., Mei, L., Zhao, Z. J., Jove, R., & Wu, J. (2004). Roles of Gab1 and SHP2 in paxillin tyrosine dephosphorylation and Src activation in response to epidermal growth factor. Journal of Biological Chemistry, 279(9), 8497–8505.PubMedCrossRef

21.

Bertotti, A., Comoglio, P. M., & Trusolino, L. (2006). Beta4 integrin activates a Shp2-Src signaling pathway that sustains HGF-induced anchorage-independent growth. Journal of Cell Biology, 175(6), 993–1003.PubMedCrossRef

22.

Klinghoffer, R. A., & Kazlauskas, A. (1995). Identification of a putative Syp substrate, the PDGF beta receptor. Journal of Biological Chemistry, 270(38), 22208–22217.PubMedCrossRef

23.

Agazie, Y. M., & Hayman, M. J. (2003). Molecular mechanism for a role of SHP2 in epidermal growth factor receptor signaling. Molecular and Cellular Biology, 23(21), 7875–7886.PubMedCrossRef

24.

Cleghon, V., Feldmann, P., Ghiglione, C., Copeland, T. D., Perrimon, N., Hughes, D. A., et al. (1998). Opposing actions of CSW and RasGAP modulate the strength of Torso RTK signaling in the Drosophila terminal pathway. Molecular Cell, 2(6), 719–727.PubMedCrossRef

25.

Hanafusa, H., Torii, S., Yasunaga, T., Matsumoto, K., & Nishida, E. (2004). Shp2, an SH2-containing protein-tyrosine phosphatase, positively regulates receptor tyrosine kinase signaling by dephosphorylating and inactivating the inhibitor Sprouty. Journal of Biological Chemistry, 279(22), 22992–22995.PubMedCrossRef

26.

Jarvis, L. A., Toering, S. J., Simon, M. A., Krasnow, M. A., & Smith-Bolton, R. K. (2006). Sprouty proteins are in vivo targets of Corkscrew/SHP-2 tyrosine phosphatases. Development, 133(6), 1133–1142.PubMedCrossRef

27.

Zhang, S. Q., Tsiaras, W. G., Araki, T., Wen, G., Minichiello, L., Klein, R., et al. (2002). Receptor-specific regulation of phosphatidylinositol 3’′-kinase activation by the protein tyrosine phosphatase Shp2. Molecular and Cellular Biology, 22(12), 4062–4072.PubMedCrossRef

28.

Mattoon, D. R., Lamothe, B., Lax, I., & Schlessinger, J. (2004). The docking protein Gab1 is the primary mediator of EGF-stimulated activation of the PI-3K/Akt cell survival pathway. BMC Biol, 2, 24.PubMedCrossRef

29.

Shi, Z. Q., Lu, W., & Feng, G. S. (1998). The Shp-2 tyrosine phosphatase has opposite effects in mediating the activation of extracellular signal-regulated and c-Jun NH2-terminal mitogen-activated protein kinases. Journal of Biological Chemistry, 273(9), 4904–4908.PubMedCrossRef

30.

You, M., Flick, L. M., Yu, D., & Feng, G. S. (2001). Modulation of the nuclear factor kappa B pathway by Shp-2 tyrosine phosphatase in mediating the induction of interleukin (IL)-6 by IL-1 or tumor necrosis factor. Journal of Experimental Medicine, 193(1), 101–110.PubMedCrossRef

31.

Schoenwaelder, S. M., Petch, L. A., Williamson, D., Shen, R., Feng, G. S., & Burridge, K. (2000). The protein tyrosine phosphatase Shp-2 regulates RhoA activity. Current Biology, 10(23), 1523–1526.PubMedCrossRef

32.

Kontaridis, M. I., Eminaga, S., Fornaro, M., Zito, C. I., Sordella, R., Settleman, J., et al. (2004). SHP-2 positively regulates myogenesis by coupling to the Rho GTPase signaling pathway. Molecular and Cellular Biology, 24(12), 5340–5352.PubMedCrossRef

33.

Uhlen, P., Burch, P. M., Zito, C. I., Estrada, M., Ehrlich, B. E., & Bennett, A. M. (2006). Gain-of-function/Noonan syndrome SHP-2/Ptpn11 mutants enhance calcium oscillations and impair NFAT signaling. Proceedings of the National Academy of Sciences of the United States of America, 103(7), 2160–2165.PubMedCrossRef

34.

Walter, A. O., Peng, Z. Y., & Cartwright, C. A. (1999). The Shp-2 tyrosine phosphatase activates the Src tyrosine kinase by a non-enzymatic mechanism. Oncogene, 18(11), 1911–1920.PubMedCrossRef

35.

Yu, W. M., Hawley, T. S., Hawley, R. G., & Qu, C. K. (2003). Catalytic-dependent and -independent roles of SHP-2 tyrosine phosphatase in interleukin-3 signaling. Oncogene, 22(38), 5995–6004.PubMedCrossRef

36.

Schubbert, S., Zenker, M., Rowe, S. L., Boll, S., Klein, C., Bollag, G., et al. (2006). Germline KRAS mutations cause Noonan syndrome. Nature Genetics, 38(3), 331–336.PubMedCrossRef

37.

Carta, C., Pantaleoni, F., Bocchinfuso, G., Stella, L., Vasta, I., Sarkozy, A., et al. (2006). Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype. American Journal of Human Genetics, 79(1), 129–135.PubMedCrossRef

38.

Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., et al. (2007). Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nature Genetics, 39(1), 70–74.PubMedCrossRef

39.

Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sarkozy, A., et al. (2007). Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nature Genetics, 39(1), 75–79.PubMedCrossRef

40.

Razzaque, M. A., Nishizawa, T., Komoike, Y., Yagi, H., Furutani, M., Amo, R., et al. (2007). Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nature Genetics, 39, 1013–1017.PubMedCrossRef

41.

Pandit, B., Sarkozy, A., Pennacchio, L. A., Carta, C., Oishi, K., Martinelli, S., et al. (2007). Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nature Genetics, 39, 1007–1012.PubMedCrossRef

42.

Tartaglia, M., Martinelli, S., Iavarone, I., Cazzaniga, G., Spinelli, M., Giarin, E., et al. (2005). Somatic PTPN11 mutations in childhood acute myeloid leukaemia. British Journal of Haematology, 129(3), 333–339.PubMedCrossRef

43.

Bentires-Alj, M., Paez, J. G., David, F. S., Keilhack, H., Halmos, B., Naoki, K., et al. (2004). Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia. Cancer Research, 64(24), 8816–8820.PubMedCrossRef

44.

Loh, M. L., Reynolds, M. G., Vattikuti, S., Gerbing, R. B., Alonzo, T. A., Carlson, E., et al. (2004). PTPN11 mutations in pediatric patients with acute myeloid leukemia: results from the Children’s Cancer Group. Leukemia, 18(11), 1831–1834.PubMedCrossRef

45.

Tartaglia, M., Martinelli, S., Cazzaniga, G., Cordeddu, V., Iavarone, I., Spinelli, M., et al. (2004). Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia. Blood, 104(2), 307–313.PubMedCrossRef

46.

Yamamoto, T., Isomura, M., Xu, Y., Liang, J., Yagasaki, H., Kamachi, Y., et al. (2006). PTPN11, RAS and FLT3 mutations in childhood acute lymphoblastic leukemia. Leukemia Research, 30(9), 1085–1089.PubMedCrossRef

47.

Martinelli, S., Carta, C., Flex, E., Binni, F., Cordisco, E. L., Moretti, S., et al. (2006). Activating PTPN11 mutations play a minor role in pediatric and adult solid tumors. Cancer Genetics and Cytogenetics, 166(2), 124–129.PubMedCrossRef

48.

Sjoblom, T., Jones, S., Wood, L. D., Parsons, D. W., Lin, J., Barber, T. D., et al. (2006). The consensus coding sequences of human breast and colorectal cancers. Science, 314(5797), 268–274.PubMedCrossRef

49.

Tartaglia, M., Kalidas, K., Shaw, A., Song, X., Musat, D. L., van der Burgt, I., et al. (2002). PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype–phenotype correlation, and phenotypic heterogeneity. American Journal of Human Genetics, 70(6), 1555–1563.PubMedCrossRef

50.

Kosaki, K., Suzuki, T., Muroya, K., Hasegawa, T., Sato, S., Matsuo, N., et al. (2002). PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) mutations in seven Japanese patients with Noonan syndrome. Journal of Clinical Endocrinology and Metabolism, 87(8), 3529–3533.PubMedCrossRef

51.

Keilhack, H., David, F. S., McGregor, M., Cantley, L. C., & Neel, B. G. (2005). Diverse biochemical properties of Shp2 mutants. Implications for disease phenotypes. Journal of Biological Chemistry, 280(35), 30984–30993.PubMedCrossRef

52.

Niihori, T., Aoki, Y., Ohashi, H., Kurosawa, K., Kondoh, T., Ishikiriyama, S., et al. (2005). Functional analysis of PTPN11/SHP-2 mutants identified in Noonan syndrome and childhood leukemia. Journal of Human Genetics, 50(4), 192–202.PubMedCrossRef

53.

Tartaglia, M., Martinelli, S., Stella, L., Bocchinfuso, G., Flex, E., Cordeddu, V., et al. (2006). Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. American Journal of Human Genetics, 78(2), 279–290.PubMedCrossRef

54.

Araki, T., Mohi, M. G., Ismat, F. A., Bronson, R. T., Williams, I. R., Kutok, J. L., et al. (2004). Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation. Nature Medicine, 10(8), 849–857.PubMedCrossRef

55.

Kontaridis, M. I., Swanson, K. D., David, F. S., Barford, D., & Neel, B. G. (2006). PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects. Journal of Biological Chemistry, 281(10), 6785–6792.PubMedCrossRef

56.

Hanna, N., Montagner, A., Lee, W. H., Miteva, M., Vidal, M., Vidaud, M., et al. (2006). Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: consequences for PI3K binding on Gab1. FEBS Letters, 580(10), 2477–2482.PubMedCrossRef

57.

Conti, E., Dottorini, T., Sarkozy, A., Tiller, G. E., Esposito, G., Pizzuti, A., et al. (2003). A novel PTPN11 mutation in LEOPARD syndrome. Human Mutation, 21(6), 654.PubMedCrossRef

58.

Brems, H., Chmara, M., Sahbatou, M., Denayer, E., Taniguchi, K., Kato, R., et al. (2007). Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. Nature Genetics, 39(9), 1120–1126.PubMedCrossRef

59.

Sarkozy, A., Conti, E., Digilio, M. C., Marino, B., Morini, E., Pacileo, G., et al. (2004). Clinical and molecular analysis of 30 patients with multiple lentigines LEOPARD syndrome. Journal of Medical Genetics, 41(5), e68.PubMedCrossRef

60.

Ucar, C., Calyskan, U., Martini, S., & Heinritz, W. (2006). Acute myelomonocytic leukemia in a boy with LEOPARD syndrome (PTPN11 gene mutation positive). Journal of Pediatric Hematology Oncology, 28(3), 123–125.CrossRef

61.

Keren, B., Hadchouel, A., Saba, S., Sznajer, Y., Bonneau, D., Leheup, B., et al. (2004). PTPN11 mutations in patients with LEOPARD syndrome: a French multicentric experience. Journal of Medical Genetics, 41(11), e117.PubMedCrossRef

62.

Merks, J. H., Caron, H. N., & Hennekam, R. C. (2005). High incidence of malformation syndromes in a series of 1,073 children with cancer. American Journal of Medical Genetics, 134(2), 132–143.PubMed

63.

Xu, R., Yu, Y., Zheng, S., Zhao, X., Dong, Q., He, Z., et al. (2005). Overexpression of Shp2 tyrosine phosphatase is implicated in leukemogenesis in adult human leukemia. Blood, 106(9), 3142–3149.PubMedCrossRef

64.

Chan, R. J., Leedy, M. B., Munugalavadla, V., Voorhorst, C. S., Li, Y., Yu, M., et al. (2005). Human somatic PTPN11 mutations induce hematopoietic-cell hypersensitivity to granulocyte-macrophage colony-stimulating factor. Blood, 105(9), 3737–3742.PubMedCrossRef

65.

Mohi, M. G., Williams, I. R., Dearolf, C. R., Chan, G., Kutok, J. L., Cohen, S., et al. (2005). Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations. Cancer Cell, 7(2), 179–191.PubMedCrossRef

66.

Yu, W. M., Daino, H., Chen, J., Bunting, K. D., & Qu, C. K. (2006). Effects of a leukemia-associated gain-of-function mutation of SHP-2 phosphatase on interleukin-3 signaling. Journal of Biological Chemistry, 281(9), 5426–5434.PubMedCrossRef

67.

Emanuel, P. D., Shannon, K. M., & Castleberry, R. P. (1996). Juvenile myelomonocytic leukemia: molecular understanding and prospects for therapy. Molecular Medicine Today, 2(11), 468–475.PubMedCrossRef

68.

Schubbert, S., Shannon, K., & Bollag, G. (2007). Hyperactive Ras in developmental disorders and cancer. Nature Reviews. Cancer, 7(4), 295–308.PubMedCrossRef

69.

Kratz, C. P., Niemeyer, C. M., Thomas, C., Bauhuber, S., Matejas, V., Bergstrasser, E., et al. (2007). Mutation analysis of Son of Sevenless in juvenile myelomonocytic leukemia. Leukemia, 21(5), 1108–1109.PubMed

70.

Schubbert, S., Lieuw, K., Rowe, S. L., Lee, C. M., Li, X., Loh, M. L., et al. (2005). Functional analysis of leukemia-associated PTPN11 mutations in primary hematopoietic cells. Blood, 106(1), 311–317.PubMedCrossRef

71.

Zhang, Y. Y., Vik, T. A., Ryder, J. W., Srour, E. F., Jacks, T., Shannon, K., et al. (1998). Nf1 regulates hematopoietic progenitor cell growth and ras signaling in response to multiple cytokines. Journal of Experimental Medicine, 187(11), 1893–1902.PubMedCrossRef

72.

Le, D. T., Kong, N., Zhu, Y., Lauchle, J. O., Aiyigari, A., Braun, B. S., et al. (2004). Somatic inactivation of Nf1 in hematopoietic cells results in a progressive myeloproliferative disorder. Blood, 103(11), 4243–4250.PubMedCrossRef

73.

Donovan, S., See, W., Bonifas, J., Stokoe, D., & Shannon, K. M. (2002). Hyperactivation of protein kinase B and ERK have discrete effects on survival, proliferation, and cytokine expression in Nf1-deficient myeloid cells. Cancer Cell, 2(6), 507–514.PubMedCrossRef

74.

Largaespada, D. A., Brannan, C. I., Jenkins, N. A., & Copeland, N. G. (1996). Nf1 deficiency causes Ras-mediated granulocyte/macrophage colony stimulating factor hypersensitivity and chronic myeloid leukaemia. Nature Genetics, 12(2), 137–143.PubMedCrossRef

75.

Bollag, G., Clapp, D. W., Shih, S., Adler, F., Zhang, Y. Y., Thompson, P., et al. (1996). Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells. Nature Genetics, 12(2), 144–148.PubMedCrossRef

76.

Braun, B. S., Tuveson, D. A., Kong, N., Le, D. T., Kogan, S. C., Rozmus, J., et al. (2004). Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder. Proceedings of the National Academy of Sciences of the United States of America, 101(2), 597–602.PubMedCrossRef

77.

Chan, I. T., Kutok, J. L., Williams, I. R., Cohen, S., Kelly, L., Shigematsu, H., et al. (2004). Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease. Journal of Clinical Investigation, 113(4), 528–538.PubMed

78.

Li, S., Gillessen, S., Tomasson, M. H., Dranoff, G., Gilliland, D. G., & Van Etten, R. A. (2001). Interleukin 3 and granulocyte-macrophage colony-stimulating factor are not required for induction of chronic myeloid leukemia-like myeloproliferative disease in mice by BCR/ABL. Blood, 97(5), 1442–1450.PubMedCrossRef

79.

Zhang, Y., Taylor, B. R., Shannon, K., & Clapp, D. W. (2001). Quantitative effects of Nf1 inactivation on in vivo hematopoiesis. Journal of Clinical Investigation, 108(5), 709–715.PubMed

80.

Chen, Y., Wen, R., Yang, S., Schuman, J., Zhang, E. E., Yi, T., et al. (2003). Identification of Shp-2 as a Stat5A phosphatase. Journal of Biological Chemistry, 278(19), 16520–16527.PubMedCrossRef

81.

Huang, W., Saberwal, G., Horvath, E., Zhu, C., Lindsey, S., & Eklund, E. A. (2006). Leukemia-associated, constitutively active mutants of SHP2 protein tyrosine phosphatase inhibit NF1 transcriptional activation by the interferon consensus sequence binding protein. Molecular and Cellular Biology, 26(17), 6311–6332.PubMedCrossRef

82.

Holtschke, T., Lohler, J., Kanno, Y., Fehr, T., Giese, N., Rosenbauer, F., et al. (1996). Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a targeted mutation of the ICSBP gene. Cell, 87(2), 307–317.PubMedCrossRef

83.

Kautz, B., Kakar, R., David, E., & Eklund, E. A. (2001). SHP1 protein-tyrosine phosphatase inhibits gp91PHOX and p67PHOX expression by inhibiting interaction of PU.1, IRF1, interferon consensus sequence-binding protein, and CREB-binding protein with homologous Cis elements in the CYBB and NCF2 genes. Journal of Biological Chemistry, 276(41), 37868–37878.PubMed

84.

Lindsey, S., Huang, W., Wang, H., Horvath, E., Zhu, C., & Eklund, E. A. (2007). Activation of SHP2 protein-tyrosine phosphatase increases HoxA10-induced repression of the genes encoding gp91(PHOX) and p67(PHOX). Journal of Biological Chemistry, 282(4), 2237–2249.PubMedCrossRef

85.

Mason, J. M., Morrison, D. J., Basson, M. A., & Licht, J. D. (2006). Sprouty proteins: multifaceted negative-feedback regulators of receptor tyrosine kinase signaling. Trends in Cell Biology, 16(1), 45–54.PubMedCrossRef

86.

Basson, M. A., Akbulut, S., Watson-Johnson, J., Simon, R., Carroll, T. J., Shakya, R., et al. (2005). Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction. Developmental Cell, 8(2), 229–239.PubMedCrossRef

87.

Taketomi, T., Yoshiga, D., Taniguchi, K., Kobayashi, T., Nonami, A., Kato, R., et al. (2005). Loss of mammalian Sprouty2 leads to enteric neuronal hyperplasia and esophageal achalasia. Nature Neuroscience, 8(7), 855–857.PubMed

88.

Shim, K., Minowada, G., Coling, D. E., & Martin, G. R. (2005). Sprouty2, a mouse deafness gene, regulates cell fate decisions in the auditory sensory epithelium by antagonizing FGF signaling. Developmental Cell, 8(4), 553–564.PubMedCrossRef

89.

Klein, O. D., Minowada, G., Peterkova, R., Kangas, A., Yu, B. D., Lesot, H., et al. (2006). Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signaling. Developmental Cell, 11(2), 181–190.PubMedCrossRef

90.

Taniguchi, K., Ayada, T., Ichiyama, K., Kohno, R., Yonemitsu, Y., Minami, Y., et al. (2007). Sprouty2 and Sprouty4 are essential for embryonic morphogenesis and regulation of FGF signaling. Biochemical and Biophysical Research Communications, 352(4), 896–902.PubMedCrossRef

91.

Wakioka, T., Sasaki, A., Kato, R., Shouda, T., Matsumoto, A., Miyoshi, K., et al. (2001). Spred is a Sprouty-related suppressor of Ras signalling. Nature, 412(6847), 647–651.PubMedCrossRef

92.

Kato, R., Nonami, A., Taketomi, T., Wakioka, T., Kuroiwa, A., Matsuda, Y., et al. (2003). Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation. Biochemical and Biophysical Research Communications, 302(4), 767–772.PubMedCrossRef

93.

Nonami, A., Kato, R., Taniguchi, K., Yoshiga, D., Taketomi, T., Fukuyama, S., et al. (2004). Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein (MAP) kinase activation in hematopoietic cells. Journal of Biological Chemistry, 279(50), 52543–52551.PubMedCrossRef

94.

Taniguchi, K., Kohno, R., Ayada, T., Kato, R., Ichiyama, K., Morisada, T., et al. (2007). Spreds are essential for embryonic lymphangiogenesis by regulating vascular endothelial growth factor receptor 3 signaling. Molecular and Cellular Biology, 27(12), 4541–4550.PubMedCrossRef

95.

Inoue, H., Kato, R., Fukuyama, S., Nonami, A., Taniguchi, K., Matsumoto, K., et al. (2005). Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness. Journal of Experimental Medicine, 201(1), 73–82.PubMedCrossRef

96.

Bundschu, K., Knobeloch, K. P., Ullrich, M., Schinke, T., Amling, M., Engelhardt, C. M., et al. (2005). Gene disruption of Spred-2 causes dwarfism. Journal of Biological Chemistry, 280(31), 28572–28580.PubMedCrossRef

97.

Nobuhisa, I., Kato, R., Inoue, H., Takizawa, M., Okita, K., Yoshimura, A., et al. (2004). Spred-2 suppresses aorta-gonad-mesonephros hematopoiesis by inhibiting MAP kinase activation. Journal of Experimental Medicine, 199(5), 737–742.PubMedCrossRef

98.

Irish, J. M., Hovland, R., Krutzik, P. O., Perez, O. D., Bruserud, O., Gjertsen, B. T., et al. (2004). Single cell profiling of potentiated phospho-protein networks in cancer cells. Cell, 118(2), 217–228.PubMedCrossRef

99.

Ornatsky, O., Baranov, V. I., Bandura, D. R., Tanner, S. D., & Dick, J. (2006). Multiple cellular antigen detection by ICP-MS. Journal of Immunological Methods, 308(1–2), 68–76.PubMedCrossRef

100.

Loh, M. L., Martinelli, S., Cordeddu, V., Reynolds, M. G., Vattikuti, S., Lee, C. M., et al. (2005). Acquired PTPN11 mutations occur rarely in adult patients with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leukemia Research, 29(4), 459–462.PubMedCrossRef

101.

Ren, R. (2005). Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. Nature Reviews. Cancer, 5(3), 172–183.PubMedCrossRef

102.

O’Hare, T., Corbin, A. S., & Druker, B. J. (2006). Targeted CML therapy: controlling drug resistance, seeking cure. Current Opinion in Genetics & Development, 16(1), 92–99.CrossRef

103.

Million, R. P., & Van Etten, R. A. (2000). The Grb2 binding site is required for the induction of chronic myeloid leukemia-like disease in mice by the Bcr/Abl tyrosine kinase. Blood, 96(2), 664–670.PubMed

104.

Zhang, X., Subrahmanyam, R., Wong, R., Gross, A. W., & Ren, R. (2001). The NH(2)-terminal coiled-coil domain and tyrosine 177 play important roles in induction of a myeloproliferative disease in mice by Bcr-Abl. Molecular and Cellular Biology, 21(3), 840–853.PubMedCrossRef

105.

He, Y., Wertheim, J. A., Xu, L., Miller, J. P., Karnell, F. G., Choi, J. K., et al. (2002). The coiled-coil domain and Tyr177 of bcr are required to induce a murine chronic myelogenous leukemia-like disease by bcr/abl. Blood, 99(8), 2957–2968.PubMedCrossRef

106.

Sattler, M., & Griffin, J. D. (2001). Mechanisms of transformation by the BCR/ABL oncogene. International Journal of Hematology, 73(3), 278–291.PubMedCrossRef

107.

Sattler, M., Mohi, M. G., Pride, Y. B., Quinnan, L. R., Malouf, N. A., Podar, K., et al. (2002). Critical role for Gab2 in transformation by BCR/ABL. Cancer Cell, 1(5), 479–492.PubMedCrossRef

108.

Scherr, M., Chaturvedi, A., Battmer, K., Dallmann, I., Schultheis, B., Ganser, A., et al. (2006). Enhanced sensitivity to inhibition of SHP2, STAT5, and Gab2 expression in chronic myeloid leukemia (CML). Blood, 107(8), 3279–3287.PubMedCrossRef

109.

Chen, J., Yu, W. M., Daino, H., Broxmeyer, H. E., Druker, B. J., & Qu, C. K. (2007). SHP-2 phosphatase is required for hematopoietic cell transformation by Bcr-Abl. Blood, 109(2), 778–785.PubMedCrossRef

110.

Teal, H. E., Ni, S., Xu, J., Finkelstein, L. D., Cheng, A. M., Paulson, R. F., et al. (2006). GRB2-mediated recruitment of GAB2, but not GAB1, to SF-STK supports the expansion of Friend virus-infected erythroid progenitor cells. Oncogene, 25(17), 2433–2443.PubMedCrossRef

111.

Ischenko, I., Petrenko, O., Gu, H., & Hayman, M. J. (2003). Scaffolding protein Gab2 mediates fibroblast transformation by the SEA tyrosine kinase. Oncogene, 22(41), 6311–6318.PubMedCrossRef

112.

Niimi, H., Harada, H., Harada, Y., Ding, Y., Imagawa, J., Inaba, T., et al. (2006). Hyperactivation of the RAS signaling pathway in myelodysplastic syndrome with AML1/RUNX1 point mutations. Leukemia, 20(4), 635–644.PubMedCrossRef

113.

Hou, H. A., Chou, W. C., Lin, L. I., Chen, C. Y., Tang, J. L., Tseng, M. H., et al. (2007). Characterization of acute myeloid leukemia with PTPN11 mutation: the mutation is closely associated with NPM1 mutation but inversely related to FLT3/ITD. Leukemia, in press. Nov 1.

114.

Yamada, K., Nishida, K., Hibi, M., Hirano, T., & Matsuda, Y. (2001). Comparative FISH mapping of Gab1 and Gab2 genes in human, mouse and rat. Cytogenetics and Cell Genetics, 94(1–2), 39–42.PubMed

115.

Bekri, S., Adelaide, J., Merscher, S., Grosgeorge, J., Caroli-Bosc, F., Perucca-Lostanlen, D., et al. (1997). Detailed map of a region commonly amplified at 11q13–>q14 in human breast carcinoma. Cytogenetics and Cell Genetics, 79(1–2), 125–131.PubMed

116.

Ormandy, C. J., Musgrove, E. A., Hui, R., Daly, R. J., & Sutherland, R. L. (2003). Cyclin D1, EMS1 and 11q13 amplification in breast cancer. Breast Cancer Research and Treatment, 78(3), 323–335.PubMedCrossRef

117.

Brummer, T., Schramek, D., Hayes, V. M., Bennett, H. L., Caldon, C. E., Musgrove, E. A., et al. (2006). Increased proliferation and altered growth factor dependence of human mammary epithelial cells overexpressing the Gab2 docking protein. Journal of Biological Chemistry, 281(1), 626–637.PubMedCrossRef

118.

Bentires-Alj, M., Gil, S. G., Chan, R., Wang, Z. C., Wang, Y., Imanaka, N., et al. (2006). A role for the scaffolding adapter GAB2 in breast cancer. Nature Medicine, 12(1), 114–121.PubMedCrossRef

119.

Ke, Y., Wu, D., Princen, F., Nguyen, T., Pang, Y., Lesperance, J., et al. (2007). Role of Gab2 in mammary tumorigenesis and metastasis. Oncogene, 26(34), 4951–4960.PubMedCrossRef

120.

Hatakeyama, M. (2004). Oncogenic mechanisms of the Helicobacter pylori CagA protein. Nature Reviews. Cancer, 4(9), 688–694.PubMedCrossRef

121.

Higashi, H., Tsutsumi, R., Muto, S., Sugiyama, T., Azuma, T., Asaka, M., et al. (2002). SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science, 295(5555), 683–686.PubMedCrossRef

122.

Tsutsumi, R., Higashi, H., Higuchi, M., Okada, M., & Hatakeyama, M. (2003). Attenuation of Helicobacter pylori CagA x SHP-2 signaling by interaction between CagA and C-terminal Src kinase. Journal of Biological Chemistry, 278(6), 3664–3670.PubMedCrossRef

123.

Higuchi, M., Tsutsumi, R., Higashi, H., & Hatakeyama, M. (2004). Conditional gene silencing utilizing the lac repressor reveals a role of SHP-2 in cagA-positive Helicobacter pylori pathogenicity. Cancer Science, 95(5), 442–447.PubMedCrossRef

124.

Tsutsumi, R., Takahashi, A., Azuma, T., Higashi, H., & Hatakeyama, M. (2006). Focal adhesion kinase is a substrate and downstream effector of SHP-2 complexed with Helicobacter pylori CagA. Molecular and Cellular Biology, 26(1), 261–276.PubMedCrossRef

125.

Manes, S., Mira, E., Gomez-Mouton, C., Zhao, Z. J., Lacalle, R. A., & Martinez, A. C. (1999). Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility. Molecular and Cellular Biology, 19(4), 3125–3135.PubMed

126.

Vadlamudi, R. K., Adam, L., Nguyen, D., Santos, M., & Kumar, R. (2002). Differential regulation of components of the focal adhesion complex by heregulin: role of phosphatase SHP-2. Journal of Cellular Physiology, 190(2), 189–199.PubMedCrossRef

127.

Oh, E. S., Gu, H., Saxton, T. M., Timms, J. F., Hausdorff, S., Frevert, E. U., et al. (1999). Regulation of early events in integrin signaling by protein tyrosine phosphatase SHP-2. Molecular and Cellular Biology, 19(4), 3205–3215.PubMed

128.

Yu, D. H., Qu, C. K., Henegariu, O., Lu, X., & Feng, G. S. (1998). Protein-tyrosine phosphatase Shp-2 regulates cell spreading, migration, and focal adhesion. Journal of Biological Chemistry, 273(33), 21125–21131.PubMedCrossRef

129.

Higashi, H., Nakaya, A., Tsutsumi, R., Yokoyama, K., Fujii, Y., Ishikawa, S., et al. (2004). Helicobacter pylori CagA induces Ras-independent morphogenetic response through SHP-2 recruitment and activation. Journal of Biological Chemistry, 279(17), 17205–17216.PubMedCrossRef

130.

Saadat, I., Higashi, H., Obuse, C., Umeda, M., Murata-Kamiya, N., Saito, Y., et al. (2007). Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity. Nature, 447(7142), 330–333.PubMedCrossRef

131.

Raabe, T., Riesgo-Escovar, J., Liu, X., Bausenwein, B. S., Deak, P., Maroy, P., et al. (1996). DOS, a novel pleckstrin homology domain-containing protein required for signal transduction between sevenless and Ras1 in Drosophila. Cell, 85(6), 911–920.PubMedCrossRef

132.

Chauhan, D., Hideshima, T., Pandey, P., Treon, S., Teoh, G., Raje, N., et al. (1999). RAFTK/PYK2-dependent and -independent apoptosis in multiple myeloma cells. Oncogene, 18(48), 6733–6740.PubMedCrossRef

133.

Agazie, Y. M., Movilla, N., Ischenko, I., & Hayman, M. J. (2003). The phosphotyrosine phosphatase SHP2 is a critical mediator of transformation induced by the oncogenic fibroblast growth factor receptor 3. Oncogene, 22(44), 6909–6918.PubMedCrossRef

134.

Bergsagel, P. L., & Kuehl, W. M. (2005). Molecular pathogenesis and a consequent classification of multiple myeloma. Journal of Clinical Oncology, 23(26), 6333–6338.PubMedCrossRef

135.

Burks, J., & Agazie, Y. M. (2006). Modulation of alpha-catenin Tyr phosphorylation by SHP2 positively effects cell transformation induced by the constitutively active FGFR3. Oncogene, 25(54), 7166–7179.PubMedCrossRef

136.

Voena, C., Conte, C., Ambrogio, C., Boeri Erba, E., Boccalatte, F., Mohammed, S., et al. (2007). The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration. Cancer Research, 67(9), 4278–4286.PubMedCrossRef

137.

Charest, A., Wilker, E. W., McLaughlin, M. E., Lane, K., Gowda, R., Coven, S., et al. (2006). ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase-2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling axis to form glioblastoma in mice. Cancer Research, 66(15), 7473–7481.PubMedCrossRef

Title: The tyrosine phosphatase Shp2 (PTPN11) in cancer
Authors: Gordon Chan
Demetrios Kalaitzidis
Benjamin G. Neel
Publication date: 01-06-2008
Publisher: Springer US
Published in: Cancer and Metastasis Reviews / Issue 2/2008
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-008-9126-y

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