MAPK pathway in congenital thyroid cancer (WP4928)

Homo sapiens

The MAPK pathway involved in the progression of different diseases such as diabetes, developmental abnormalities and cancer since it has a essential role in the regulation a wide variety of cellular processes such as proliferation, differentiation and apoptosis. consequently, dysregulation of MAPK pathway leads to the occurrence of the related disease

Authors

Omran Hasan , Egon Willighagen , Friederike Ehrhart , Eric Weitz , and Alex Pico

Activity

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

altered Erk5 MAPK signaling pathway thyroid cancer pathway

Disease Ontology

thyroid gland cancer

Participants

Label Type Compact URI Comment
GTP Metabolite chebi:15996
GDP Metabolite chebi:17552
KSR1 GeneProduct ensembl:ENSG00000141068
MAP2K2 GeneProduct ensembl:ENSG00000126934
ELK1 GeneProduct ensembl:ENSG00000126767
c-FOS GeneProduct ensembl:ENSG00000170345
c-MYC GeneProduct ensembl:ENSG00000136997
c-JUN GeneProduct ensembl:ENSG00000177606
CRAF GeneProduct ensembl:ENSG00000132155
MAP2K1 GeneProduct ensembl:ENSG00000169032
SOS2 GeneProduct ensembl:ENSG00000100485
MAPK3 GeneProduct ensembl:ENSG00000102882 Also known as ERK
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MAPK3 GeneProduct ensembl:ENSG00000102882 Also known as ERK
SHC1 GeneProduct ensembl:ENSG00000160691
BRAF GeneProduct ensembl:ENSG00000157764
SOS1 GeneProduct ensembl:ENSG00000115904
RAS Protein ensembl:ENSG00000133703 RAS protein has three isoforms ( K,N and H RAS). the isoforms differ in ability of activating RAF protein, the isoform which is responsable the most of activating of Raf protein is Kras> also, HRAS has the ability of activating the RAF proteins but less efficiently than KRAS. (PMID: 9727023)
ALK tyrosine kinase receptor Protein uniprot:Q9UM73
GRB2 Protein uniprot:Q75VX8

References

  1. B-raf, a new member of the raf family, is activated by DNA rearrangement. Ikawa S, Fukui M, Ueyama Y, Tamaoki N, Yamamoto T, Toyoshima K. Mol Cell Biol. 1988 Jun;8(6):2651–4. PubMed Europe PMC Scholia
  2. The ras gene family and human carcinogenesis. Bos JL. Mutat Res. 1988 May;195(3):255–71. PubMed Europe PMC Scholia
  3. Detection of activated ras oncogenes in human thyroid carcinomas. Suárez HG, Du Villard JA, Caillou B, Schlumberger M, Tubiana M, Parmentier C, et al. Oncogene. 1988 Apr;2(4):403–6. PubMed Europe PMC Scholia
  4. Characterization of murine A-raf, a new oncogene related to the v-raf oncogene. Huleihel M, Goldsborough M, Cleveland J, Gunnell M, Bonner T, Rapp UR. Mol Cell Biol. 1986 Jul;6(7):2655–62. PubMed Europe PMC Scholia
  5. Structure and biological activity of v-raf, a unique oncogene transduced by a retrovirus. Rapp UR, Goldsborough MD, Mark GE, Bonner TI, Groffen J, Reynolds FH Jr, et al. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4218–22. PubMed Europe PMC Scholia
  6. Ras isoforms vary in their ability to activate Raf-1 and phosphoinositide 3-kinase. Yan J, Roy S, Apolloni A, Lane A, Hancock JF. J Biol Chem. 1998 Sep 11;273(37):24052–6. PubMed Europe PMC Scholia
  7. Prevalence of Ras mutations in thyroid neoplasia. Esapa CT, Johnson SJ, Kendall-Taylor P, Lennard TW, Harris PE. Clin Endocrinol (Oxf). 1999 Apr;50(4):529–35. PubMed Europe PMC Scholia
  8. Gene rearrangement and Chernobyl related thyroid cancers. Santoro M, Thomas GA, Vecchio G, Williams GH, Fusco A, Chiappetta G, et al. Br J Cancer. 2000 Jan;82(2):315–22. PubMed Europe PMC Scholia
  9. The RAS oncogene induces genomic instability in thyroid PCCL3 cells via the MAPK pathway. Saavedra HI, Knauf JA, Shirokawa JM, Wang J, Ouyang B, Elisei R, et al. Oncogene. 2000 Aug 10;19(34):3948–54. PubMed Europe PMC Scholia
  10. Differential activation of the Rac pathway by Ha-Ras and K-Ras. Walsh AB, Bar-Sagi D. J Biol Chem. 2001 May 11;276(19):15609–15. PubMed Europe PMC Scholia
  11. Identification of anaplastic lymphoma kinase as a receptor for the growth factor pleiotrophin. Stoica GE, Kuo A, Aigner A, Sunitha I, Souttou B, Malerczyk C, et al. J Biol Chem. 2001 May 18;276(20):16772–9. PubMed Europe PMC Scholia
  12. RET/PTC rearrangement in thyroid tumors. Nikiforov YE. Endocr Pathol. 2002;13(1):3–16. PubMed Europe PMC Scholia
  13. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA. Cancer Res. 2003 Apr 1;63(7):1454–7. PubMed Europe PMC Scholia
  14. Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations. Zhu Z, Gandhi M, Nikiforova MN, Fischer AH, Nikiforov YE. Am J Clin Pathol. 2003 Jul;120(1):71–7. PubMed Europe PMC Scholia
  15. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. Nikiforova MN, Kimura ET, Gandhi M, Biddinger PW, Knauf JA, Basolo F, et al. J Clin Endocrinol Metab. 2003 Nov;88(11):5399–404. PubMed Europe PMC Scholia
  16. Regulation of Raf-1 by direct feedback phosphorylation. Dougherty MK, Müller J, Ritt DA, Zhou M, Zhou XZ, Copeland TD, et al. Mol Cell. 2005 Jan 21;17(2):215–24. PubMed Europe PMC Scholia
  17. Conditional BRAFV600E expression induces DNA synthesis, apoptosis, dedifferentiation, and chromosomal instability in thyroid PCCL3 cells. Mitsutake N, Knauf JA, Mitsutake S, Mesa C Jr, Zhang L, Fagin JA. Cancer Res. 2005 Mar 15;65(6):2465–73. PubMed Europe PMC Scholia
  18. RET tyrosine kinase signaling in development and cancer. Arighi E, Borrello MG, Sariola H. Cytokine Growth Factor Rev. 2005;16(4–5):441–67. PubMed Europe PMC Scholia
  19. Thyroid targeting of the N-ras(Gln61Lys) oncogene in transgenic mice results in follicular tumors that progress to poorly differentiated carcinomas. Vitagliano D, Portella G, Troncone G, Francione A, Rossi C, Bruno A, et al. Oncogene. 2006 Aug 31;25(39):5467–74. PubMed Europe PMC Scholia
  20. The MEK/ERK cascade: from signaling specificity to diverse functions. Shaul YD, Seger R. Biochim Biophys Acta. 2007 Aug;1773(8):1213–26. PubMed Europe PMC Scholia
  21. GEFs and GAPs: critical elements in the control of small G proteins. Bos JL, Rehmann H, Wittinghofer A. Cell. 2007 Jun 1;129(5):865–77. PubMed Europe PMC Scholia
  22. Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven tumorigenesis in mice. Gupta S, Ramjaun AR, Haiko P, Wang Y, Warne PH, Nicke B, et al. Cell. 2007 Jun 1;129(5):957–68. PubMed Europe PMC Scholia
  23. The complexity of mitogen-activated protein kinases (MAPKs) made simple. Krishna M, Narang H. Cell Mol Life Sci. 2008 Nov;65(22):3525–44. PubMed Europe PMC Scholia
  24. Impact of feedback phosphorylation and Raf heterodimerization on normal and mutant B-Raf signaling. Ritt DA, Monson DM, Specht SI, Morrison DK. Mol Cell Biol. 2010 Feb;30(3):806–19. PubMed Europe PMC Scholia
  25. Ras trafficking, localization and compartmentalized signalling. Prior IA, Hancock JF. Semin Cell Dev Biol. 2012 Apr;23(2):145–53. PubMed Europe PMC Scholia
  26. A comprehensive survey of Ras mutations in cancer. Prior IA, Lewis PD, Mattos C. Cancer Res. 2012 May 15;72(10):2457–67. PubMed Europe PMC Scholia
  27. Drugging the undruggable RAS: Mission possible? Cox AD, Fesik SW, Kimmelman AC, Luo J, Der CJ. Nat Rev Drug Discov. 2014 Nov;13(11):828–51. PubMed Europe PMC Scholia
  28. Regulation of RAF protein kinases in ERK signalling. Lavoie H, Therrien M. Nat Rev Mol Cell Biol. 2015 May;16(5):281–98. PubMed Europe PMC Scholia
  29. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. Landa I, Ibrahimpasic T, Boucai L, Sinha R, Knauf JA, Shah RH, et al. J Clin Invest. 2016 Mar 1;126(3):1052–66. PubMed Europe PMC Scholia
  30. TERT, BRAF, and NRAS in Primary Thyroid Cancer and Metastatic Disease. Melo M, Gaspar da Rocha A, Batista R, Vinagre J, Martins MJ, Costa G, et al. J Clin Endocrinol Metab. 2017 Jun 1;102(6):1898–907. PubMed Europe PMC Scholia
  31. MEK drives BRAF activation through allosteric control of KSR proteins. Lavoie H, Sahmi M, Maisonneuve P, Marullo SA, Thevakumaran N, Jin T, et al. Nature. 2018 Feb 22;554(7693):549–53. PubMed Europe PMC Scholia
  32. The Interdependent Activation of Son-of-Sevenless and Ras. Bandaru P, Kondo Y, Kuriyan J. Cold Spring Harb Perspect Med. 2019 Feb 1;9(2):a031534. PubMed Europe PMC Scholia