MAPK pathway in congenital thyroid cancer (Homo sapiens)

From WikiPathways

Jump to: navigation, search
14, 18, 1942, 25, 3024, 28KSR124NucleusCytoplasmMAP2K23, 1912, 1914, 19, 284, 1214, 19, 289, 12, 1920, 2323, 2814, 1914, 193, 1923, 28ELK1c-FOSc-MYCc-JUNCRAFRASGTP1, 5, 7, 10-13, 15...MAP2K1SOS218MAPK31918, 20ALK tyrosine kinase receptor3, 6, 8, 17, 19GDPMAPK3SHC118, 203BRAF18, 20-22, 28...SOS1GRB2193


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

Quality Tags

Ontology Terms



View all...
  1. Esapa CT, Johnson SJ, Kendall-Taylor P, Lennard TW, Harris PE; ''Prevalence of Ras mutations in thyroid neoplasia.''; Clin Endocrinol (Oxf), 1999 PubMed Europe PMC Scholia
  2. Rapp UR, Goldsborough MD, Mark GE, Bonner TI, Groffen J, Reynolds FH Jr, Stephenson JR; ''Structure and biological activity of v-raf, a unique oncogene transduced by a retrovirus.''; Proc Natl Acad Sci U S A, 1983 PubMed Europe PMC Scholia
  3. Arighi E, Borrello MG, Sariola H; ''RET tyrosine kinase signaling in development and cancer.''; Cytokine Growth Factor Rev, 2005 PubMed Europe PMC Scholia
  4. Bos JL, Rehmann H, Wittinghofer A; ''GEFs and GAPs: critical elements in the control of small G proteins.''; Cell, 2007 PubMed Europe PMC Scholia
  5. Zhu Z, Gandhi M, Nikiforova MN, Fischer AH, Nikiforov YE; ''Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations.''; Am J Clin Pathol, 2003 PubMed Europe PMC Scholia
  6. Nikiforov YE; ''RET/PTC rearrangement in thyroid tumors.''; Endocr Pathol, 2002 PubMed Europe PMC Scholia
  7. Prior IA, Hancock JF; ''Ras trafficking, localization and compartmentalized signalling.''; Semin Cell Dev Biol, 2012 PubMed Europe PMC Scholia
  8. Santoro M, Thomas GA, Vecchio G, Williams GH, Fusco A, Chiappetta G, Pozcharskaya V, Bogdanova TI, Demidchik EP, Cherstvoy ED, Voscoboinik L, Tronko ND, Carss A, Bunnell H, Tonnachera M, Parma J, Dumont JE, Keller G, Höfler H, Williams ED; ''Gene rearrangement and Chernobyl related thyroid cancers.''; Br J Cancer, 2000 PubMed Europe PMC Scholia
  9. Bandaru P, Kondo Y, Kuriyan J; ''The Interdependent Activation of Son-of-Sevenless and Ras.''; Cold Spring Harb Perspect Med, 2019 PubMed Europe PMC Scholia
  10. Bos JL; ''The ras gene family and human carcinogenesis.''; Mutat Res, 1988 PubMed Europe PMC Scholia
  11. Prior IA, Lewis PD, Mattos C; ''A comprehensive survey of Ras mutations in cancer.''; Cancer Res, 2012 PubMed Europe PMC Scholia
  12. Cox AD, Fesik SW, Kimmelman AC, Luo J, Der CJ; ''Drugging the undruggable RAS: Mission possible?''; Nat Rev Drug Discov, 2014 PubMed Europe PMC Scholia
  13. Vitagliano D, Portella G, Troncone G, Francione A, Rossi C, Bruno A, Giorgini A, Coluzzi S, Nappi TC, Rothstein JL, Pasquinelli R, Chiappetta G, Terracciano D, Macchia V, Melillo RM, Fusco A, Santoro M; ''Thyroid targeting of the N-ras(Gln61Lys) oncogene in transgenic mice results in follicular tumors that progress to poorly differentiated carcinomas.''; Oncogene, 2006 PubMed Europe PMC Scholia
  14. Krishna M, Narang H; ''The complexity of mitogen-activated protein kinases (MAPKs) made simple.''; Cell Mol Life Sci, 2008 PubMed Europe PMC Scholia
  15. Yan J, Roy S, Apolloni A, Lane A, Hancock JF; ''Ras isoforms vary in their ability to activate Raf-1 and phosphoinositide 3-kinase.''; J Biol Chem, 1998 PubMed Europe PMC Scholia
  16. Gupta S, Ramjaun AR, Haiko P, Wang Y, Warne PH, Nicke B, Nye E, Stamp G, Alitalo K, Downward J; ''Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven tumorigenesis in mice.''; Cell, 2007 PubMed Europe PMC Scholia
  17. Stoica GE, Kuo A, Aigner A, Sunitha I, Souttou B, Malerczyk C, Caughey DJ, Wen D, Karavanov A, Riegel AT, Wellstein A; ''Identification of anaplastic lymphoma kinase as a receptor for the growth factor pleiotrophin.''; J Biol Chem, 2001 PubMed Europe PMC Scholia
  18. Mitsutake N, Knauf JA, Mitsutake S, Mesa C Jr, Zhang L, Fagin JA; ''Conditional BRAFV600E expression induces DNA synthesis, apoptosis, dedifferentiation, and chromosomal instability in thyroid PCCL3 cells.''; Cancer Res, 2005 PubMed Europe PMC Scholia
  19. Shaul YD, Seger R; ''The MEK/ERK cascade: from signaling specificity to diverse functions.''; Biochim Biophys Acta, 2007 PubMed Europe PMC Scholia
  20. Ritt DA, Monson DM, Specht SI, Morrison DK; ''Impact of feedback phosphorylation and Raf heterodimerization on normal and mutant B-Raf signaling.''; Mol Cell Biol, 2010 PubMed Europe PMC Scholia
  21. Melo M, Gaspar da Rocha A, Batista R, Vinagre J, Martins MJ, Costa G, Ribeiro C, Carrilho F, Leite V, Lobo C, Cameselle-Teijeiro JM, Cavadas B, Pereira L, Sobrinho-Simões M, Soares P; ''TERT, BRAF, and NRAS in Primary Thyroid Cancer and Metastatic Disease.''; J Clin Endocrinol Metab, 2017 PubMed Europe PMC Scholia
  22. Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA; ''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.''; Cancer Res, 2003 PubMed Europe PMC Scholia
  23. Dougherty MK, Müller J, Ritt DA, Zhou M, Zhou XZ, Copeland TD, Conrads TP, Veenstra TD, Lu KP, Morrison DK; ''Regulation of Raf-1 by direct feedback phosphorylation.''; Mol Cell, 2005 PubMed Europe PMC Scholia
  24. Lavoie H, Sahmi M, Maisonneuve P, Marullo SA, Thevakumaran N, Jin T, Kurinov I, Sicheri F, Therrien M; ''MEK drives BRAF activation through allosteric control of KSR proteins.''; Nature, 2018 PubMed Europe PMC Scholia
  25. Ikawa S, Fukui M, Ueyama Y, Tamaoki N, Yamamoto T, Toyoshima K; ''B-raf, a new member of the raf family, is activated by DNA rearrangement.''; Mol Cell Biol, 1988 PubMed Europe PMC Scholia
  26. Suárez HG, Du Villard JA, Caillou B, Schlumberger M, Tubiana M, Parmentier C, Monier R; ''Detection of activated ras oncogenes in human thyroid carcinomas.''; Oncogene, 1988 PubMed Europe PMC Scholia
  27. Saavedra HI, Knauf JA, Shirokawa JM, Wang J, Ouyang B, Elisei R, Stambrook PJ, Fagin JA; ''The RAS oncogene induces genomic instability in thyroid PCCL3 cells via the MAPK pathway.''; Oncogene, 2000 PubMed Europe PMC Scholia
  28. Lavoie H, Therrien M; ''Regulation of RAF protein kinases in ERK signalling.''; Nat Rev Mol Cell Biol, 2015 PubMed Europe PMC Scholia
  29. Landa I, Ibrahimpasic T, Boucai L, Sinha R, Knauf JA, Shah RH, Dogan S, Ricarte-Filho JC, Krishnamoorthy GP, Xu B, Schultz N, Berger MF, Sander C, Taylor BS, Ghossein R, Ganly I, Fagin JA; ''Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers.''; J Clin Invest, 2016 PubMed Europe PMC Scholia
  30. Huleihel M, Goldsborough M, Cleveland J, Gunnell M, Bonner T, Rapp UR; ''Characterization of murine A-raf, a new oncogene related to the v-raf oncogene.''; Mol Cell Biol, 1986 PubMed Europe PMC Scholia
  31. Walsh AB, Bar-Sagi D; ''Differential activation of the Rac pathway by Ha-Ras and K-Ras.''; J Biol Chem, 2001 PubMed Europe PMC Scholia
  32. Nikiforova MN, Kimura ET, Gandhi M, Biddinger PW, Knauf JA, Basolo F, Zhu Z, Giannini R, Salvatore G, Fusco A, Santoro M, Fagin JA, Nikiforov YE; ''BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas.''; J Clin Endocrinol Metab, 2003 PubMed Europe PMC Scholia


View all...
111017view05:59, 30 June 2020FehrhartOntology Term : 'thyroid cancer' added !
111016view05:58, 30 June 2020FehrhartOntology Term : 'thyroid cancer pathway' added !
111015view05:58, 30 June 2020FehrhartOntology Term : 'altered Erk5 MAPK signaling pathway' added !
111014view05:57, 30 June 2020FehrhartOntology Term : 'Pathway Ontology' added !
111007view06:16, 29 June 2020FehrhartModified title
111002view17:42, 26 June 2020Omranhasanrename Nucleus
110897view11:21, 18 June 2020OmranhasanModified description
110880view11:38, 17 June 2020OmranhasanAdd a KSR1 scaffolding protein with references
110838view09:15, 12 June 2020Omranhasanvisualization
110833view22:19, 11 June 2020Omranhasanadding annotation to the pathway components add visualization
110826view11:19, 10 June 2020Omranhasan_ redrawing the (GDP=>GTP) interaction _adding references to the interactions
110778view11:18, 4 June 2020Omranhasanconnecting nodes
110777view09:23, 4 June 2020Omranhasanconnecting tyrosine kinase receptor to the the adopter proteins ( GRB2,SHC1)
110771view20:56, 3 June 2020EgonwReplaced a secondary ChEBI identifiers with a primary identifier.
110769view13:16, 3 June 2020Omranhasantest
110680view11:18, 28 May 2020Fehrharttest2
110679view11:15, 28 May 2020Fehrharttest
110678view11:14, 28 May 2020Fehrhartconnected a line for test
110520view06:48, 17 May 2020EgonwReplaced a secondary ChEBI identifiers with a primary identifier.
110505view11:53, 15 May 2020OmranhasanNew pathway

External references


View all...
NameTypeDatabase referenceComment


ProteinENSG00000133703 (Ensembl) 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 receptorProteinQ9UM73 (Uniprot-TrEMBL)
BRAFGeneProductENSG00000157764 (Ensembl)
CRAF GeneProductENSG00000132155 (Ensembl)
ELK1GeneProductENSG00000126767 (Ensembl)
GDPMetaboliteCHEBI:17552 (ChEBI)
GRB2ProteinQ75VX8 (Uniprot-TrEMBL)
GTPMetaboliteCHEBI:15996 (ChEBI)
KSR1GeneProductENSG00000141068 (Ensembl)
MAP2K1GeneProductENSG00000169032 (Ensembl)
MAP2K2GeneProductENSG00000126934 (Ensembl)
MAPK3 GeneProductENSG00000102882 (Ensembl) Also known as ERK
MAPK3GeneProductENSG00000102882 (Ensembl)
  • Also known as ERK
  • Type your comment here
SHC1GeneProductENSG00000160691 (Ensembl)
SOS1GeneProductENSG00000115904 (Ensembl)
SOS2GeneProductENSG00000100485 (Ensembl)
c-FOSGeneProductENSG00000170345 (Ensembl)
c-JUNGeneProductENSG00000177606 (Ensembl)
c-MYCGeneProductENSG00000136997 (Ensembl)

Annotated Interactions

No annotated interactions

Personal tools