KEGG   PATHWAY: ko04014
Entry
ko04014                     Pathway                                
Name
Ras signaling pathway
Description
The Ras proteins are GTPases that function as molecular switches for signaling pathways regulating cell proliferation, survival, growth, migration, differentiation or cytoskeletal dynamism. Ras proteins transduce signals from extracellular growth factors by cycling between inactive GDP-bound and active GTP-bound states. The exchange of GTP for GDP on RAS is regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Activated RAS (RAS-GTP) regulates multiple cellular functions through effectors including Raf, phosphatidylinositol 3-kinase (PI3K) and Ral guanine nucleotide-dissociation stimulator (RALGDS).
Class
Environmental Information Processing; Signal transduction
Pathway map
ko04014  Ras signaling pathway
ko04014

Other DBs
GO: 0032318
Orthology
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01047  PLA2G, SPLA2; secretory phospholipase A2 [EC:3.1.1.4]
K01115  PLD1_2; phospholipase D1/2 [EC:3.1.4.4]
K01116  PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11]
K02158  BAD; Bcl-2-antagonist of cell death
K02183  CALM; calmodulin
K02580  NFKB1; nuclear factor NF-kappa-B p105 subunit
K02582  NGFB; nerve growth factor, beta
K02583  NGFR, TNFRSF16, CD271; tumor necrosis factor receptor superfamily member 16
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02677  PRKCA; classical protein kinase C alpha type [EC:2.7.11.13]
K02678  ETS1, pnt; C-ets-1
K02833  HRAS; GTPase HRas
K03099  SOS; son of sevenless
K03176  NTRK1, TRKA; neurotrophic tyrosine kinase receptor type 1 [EC:2.7.10.1]
K04163  HTR7; 5-hydroxytryptamine receptor 7
K04345  PKA; protein kinase A [EC:2.7.11.11]
K04347  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04349  RASGRF1; Ras-specific guanine nucleotide-releasing factor 1
K04350  RASGRP1; RAS guanyl-releasing protein 1
K04352  RASA1, RASGAP; Ras GTPase-activating protein 1
K04353  RAP1A; Ras-related protein Rap-1A
K04355  BDNF; brain-derived neurotrophic factor
K04356  NTF3; neurotrophin 3
K04357  EGF; epidermal growth factor
K04358  FGF; fibroblast growth factor
K04359  PDGFA; platelet-derived growth factor subunit A
K04360  NTRK2, TRKB; neurotrophic tyrosine kinase receptor type 2 [EC:2.7.10.1]
K04361  EGFR, ERBB1; epidermal growth factor receptor [EC:2.7.10.1]
K04362  FGFR1, CD331; fibroblast growth factor receptor 1 [EC:2.7.10.1]
K04363  PDGFRA, CD140A; platelet-derived growth factor receptor alpha [EC:2.7.10.1]
K04364  GRB2; growth factor receptor-bound protein 2
K04366  RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04375  ELK1; ETS domain-containing protein Elk-1
K04389  TNFSF6, FASL, CD178; tumor necrosis factor ligand superfamily member 6
K04392  RAC1; Ras-related C3 botulinum toxin substrate 1
K04393  CDC42; cell division control protein 42
K04409  PAK1; p21-activated kinase 1 [EC:2.7.11.1]
K04410  PAK2; p21-activated kinase 2 [EC:2.7.11.1]
K04411  STK4, MST1; serine/threonine kinase 4
K04440  JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04467  IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K04513  RHOA; Ras homolog gene family, member A
K04526  INS; insulin
K04527  INSR, CD220; insulin receptor [EC:2.7.10.1]
K04536  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04537  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
K04538  GNB4; guanine nucleotide-binding protein subunit beta-4
K04539  GNB5; guanine nucleotide-binding protein subunit beta-5
K04540  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
K04541  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
K04542  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
K04543  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04544  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
K04545  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
K04546  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
K04547  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04548  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1
K04549  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
K04570  BCL2L1, bcl-xL; Bcl-2-like 1 (apoptosis regulator Bcl-X)
K04735  RELA; transcription factor p65
K05087  IGF1R, CD221; insulin-like growth factor 1 receptor [EC:2.7.10.1]
K05089  PDGFRB, CD140B; platelet-derived growth factor receptor beta [EC:2.7.10.1]
K05090  CSF1R, FMS, CD115; macrophage colony-stimulating factor 1 receptor [EC:2.7.10.1]
K05091  KIT, SCFR, CD117; proto-oncogene tyrosine-protein kinase Kit [EC:2.7.10.1]
K05092  FLT3, FLK2, CD135; fms-related tyrosine kinase 3 [EC:2.7.10.1]
K05093  FGFR2, CD332; fibroblast growth factor receptor 2 [EC:2.7.10.1]
K05094  FGFR3, CD333; fibroblast growth factor receptor 3 [EC:2.7.10.1]
K05095  FGFR4, CD334; fibroblast growth factor receptor 4 [EC:2.7.10.1]
K05096  FLT1, VEGFR1; FMS-like tyrosine kinase 1 [EC:2.7.10.1]
K05097  FLT4, VEGFR3; FMS-like tyrosine kinase 4 [EC:2.7.10.1]
K05098  KDR, VEGFR2, CD309; kinase insert domain protein receptor [EC:2.7.10.1]
K05099  MET, HGFR; proto-oncogene tyrosine-protein kinase Met [EC:2.7.10.1]
K05103  EPHA2, ECK; Eph receptor A2 [EC:2.7.10.1]
K05121  TEK, TIE2, CD202; endothelial-specific receptor tyrosine kinase [EC:2.7.10.1]
K05208  GRIN1; glutamate receptor ionotropic, NMDA 1
K05209  GRIN2A; glutamate receptor ionotropic, NMDA 2A
K05210  GRIN2B; glutamate receptor ionotropic, NMDA 2B
K05410  TBK1; TANK-binding kinase 1 [EC:2.7.11.10]
K05448  VEGFA; vascular endothelial growth factor A
K05449  VEGFC_D; vascular endothelial growth factor C/D
K05450  PDGFC_D; platelet derived growth factor C/D
K05451  NGFA; nerve growth factor, alpha
K05453  CSF1, MCSF; macrophage colony-stimulating factor 1
K05454  FLT3LG; fms-related tyrosine kinase 3 ligand
K05459  IGF1; insulin-like growth factor 1
K05460  HGF; hepatocyte growth factor
K05461  KITLG; KIT ligand
K05462  EFNA; ephrin-A
K05465  ANGPT1; angiopoietin 1
K05466  ANGPT2; angiopoietin 2
K05467  ANGPT4; angiopoietin 4
K05702  AF6, MLLT4; afadin
K05731  TIAM1; T-lymphoma invasion and metastasis-inducing protein 1
K05733  PAK3, MRX30; p21-activated kinase 3 [EC:2.7.11.1]
K05734  PAK4; p21-activated kinase 4 [EC:2.7.11.1]
K05735  PAK6; p21-activated kinase 6 [EC:2.7.11.1]
K05736  PAK5, PAK7; p21-activated kinase 5 [EC:2.7.11.1]
K05859  PLCG2; phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11]
K05860  PLCE; phosphatidylinositol phospholipase C, epsilon [EC:3.1.4.11]
K06279  SHC1; SHC-transforming protein 1
K06619  ABL1; abelson tyrosine-protein kinase 1 [EC:2.7.10.2]
K07209  IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K07210  IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K07293  PTPN11, SHP2; tyrosine-protein phosphatase non-receptor type 11 [EC:3.1.3.48]
K07360  ZAP70; tyrosine-protein kinase ZAP-70 [EC:2.7.10.2]
K07362  LAT; linker for activation of T cells family member 1
K07825  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
K07826  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
K07827  KRAS, KRAS2; GTPase KRas
K07828  NRAS; GTPase NRas
K07829  RRAS; Ras-related protein R-Ras
K07830  RRAS2, TC21; Ras-related protein R-Ras2
K07831  MRAS; Ras-related protein M-Ras
K07834  RALA; Ras-related protein Ral-A
K07835  RALB; Ras-related protein Ral-B
K07836  RAP1B; Ras-related protein Rap-1B
K07860  RAC2; Ras-related C3 botulinum toxin substrate 2
K07861  RAC3; Ras-related C3 botulinum toxin substrate 3
K07887  RAB5A; Ras-related protein Rab-5A
K07888  RAB5B; Ras-related protein Rab-5B
K07889  RAB5C; Ras-related protein Rab-5C
K07941  ARF6; ADP-ribosylation factor 6
K08015  RASSF5, RAPL; Ras association domain-containing protein 5
K08019  RAPGEF5; Rap guanine nucleotide exchange factor 5
K08052  NF1; neurofibromin 1
K08053  RASA2, GAP1M; Ras GTPase-activating protein 2
K08091  GAB2; GRB2-associated-binding protein 2
K08732  RALGDS; ral guanine nucleotide dissociation stimulator
K08773  RALBP1; RalA-binding protein 1
K08774  TGFA; transforming growth factor, alpha
K08887  ABL2; abelson tyrosine-protein kinase 2 [EC:2.7.10.2]
K09254  REL; c-Rel proto-oncogene protein
K09593  GAB1; GRB2-associated-binding protein 1
K09850  RASSF1; Ras association domain-containing protein 1
K10632  BRAP; BRCA1-associated protein [EC:2.3.2.27]
K10784  TRAV; T cell receptor alpha chain V region
K10785  TRBV; T-cell receptor beta chain V region
K12326  RASGRF2; Ras-specific guanine nucleotide-releasing factor 2
K12358  FOXO4; forkhead box protein O4
K12361  RASGRP2; RAS guanyl-releasing protein 2
K12362  RASGRP3; RAS guanyl-releasing protein 3
K12363  RASGRP4; RAS guanyl-releasing protein 4
K12380  RASA3; Ras GTPase-activating protein 3
K12457  NTF4; neurotrophin 4
K13618  PLA1A; phosphatidylserine sn-1 acylhydrolase [EC:3.1.1.111]
K13769  IGF2; insulin-like growth factor 2
K14958  KSR1; kinase suppressor of Ras 1
K16342  PLA2G4, CPLA2; cytosolic phospholipase A2 [EC:3.1.1.4]
K16343  PLA2G6, IPLA2; calcium-independent phospholipase A2 [EC:3.1.1.4]
K16817  PLA2G16; HRAS-like suppressor 3 [EC:3.1.1.32 3.1.1.4]
K16858  VEGFB; vascular endothelial growth factor B
K16859  PGF; placenta growth factor
K17386  PDGFB; platelet-derived growth factor subunit B
K17447  SHC2; SHC-transforming protein 2
K17448  SHC3; SHC-transforming protein 3
K17449  SHC4; SHC-transforming protein 4
K17630  RASA4, CAPRI; Ras GTPase-activating protein 4
K17631  SYNGAP, RASA5; Ras/Rap GTPase-activating protein SynGAP
K17632  RASAL1; RAS protein activator-like 1
K17633  RASAL2; RAS protein activator-like 2
K17634  RASAL3; RAS protein activator-like 3
K17635  RGL1, RGL; ral guanine nucleotide dissociation stimulator-like 1
K17636  RGL2; ral guanine nucleotide dissociation stimulator-like 2
K17637  EXOC2, SEC5; exocyst complex component 2
K17638  RIN1; Ras and Rab interactor 1
K18496  FGF1; fibroblast growth factor 1
K18497  FGF2; fibroblast growth factor 2
K18529  KSR2; kinase suppressor of Ras 2 [EC:2.7.11.1]
K19613  SHOC2, SUR8; leucine-rich repeat protein SHOC2
K19662  PRKCB; classical protein kinase C beta type [EC:2.7.11.13]
K19663  PRKCG; classical protein kinase C gamma type [EC:2.7.11.13]
K21932  ETS2; C-ets-2
K22428  FGF23; fibroblast growth factor 23
K22429  FGF21; fibroblast growth factor 21
K22603  FGF19; fibroblast growth factor 19
K25768  RALGAPA; Ral GTPase-activating protein subunit alpha
K25769  RALGAPB; Ral GTPase-activating protein subunit beta
Compound
C00035  GDP
C00044  GTP
C00076  Calcium cation
C00165  Diacylglycerol
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:18568040
  Authors
Karnoub AE, Weinberg RA
  Title
Ras oncogenes: split personalities.
  Journal
Nat Rev Mol Cell Biol 9:517-31 (2008)
DOI:10.1038/nrm2438
Reference
PMID:12778136
  Authors
Malumbres M, Barbacid M
  Title
RAS oncogenes: the first 30 years.
  Journal
Nat Rev Cancer 3:459-65 (2003)
DOI:10.1038/nrc1097
Reference
PMID:21686117
  Authors
Cox AD, Der CJ
  Title
Ras history: The saga continues.
  Journal
Small GTPases 1:2-27 (2010)
DOI:10.4161/sgtp.1.1.12178
Reference
PMID:12642680
  Authors
Cox AD, Der CJ
  Title
Ras family signaling: therapeutic targeting.
  Journal
Cancer Biol Ther 1:599-606 (2002)
DOI:10.4161/cbt.306
Reference
PMID:17428555
  Authors
Rajalingam K, Schreck R, Rapp UR, Albert S
  Title
Ras oncogenes and their downstream targets.
  Journal
Biochim Biophys Acta 1773:1177-95 (2007)
DOI:10.1016/j.bbamcr.2007.01.012
Reference
PMID:17384584
  Authors
Schubbert S, Shannon K, Bollag G
  Title
Hyperactive Ras in developmental disorders and cancer.
  Journal
Nat Rev Cancer 7:295-308 (2007)
DOI:10.1038/nrc2109
Reference
PMID:22233291
  Authors
Poulogiannis G, Luo F, Arends MJ
  Title
RAS signalling in the colorectum in health and disease.
  Journal
Cell Commun Adhes 19:1-9 (2012)
DOI:10.3109/15419061.2011.649380
Reference
PMID:22020205
  Authors
Berndt N, Hamilton AD, Sebti SM
  Title
Targeting protein prenylation for cancer therapy.
  Journal
Nat Rev Cancer 11:775-91 (2011)
DOI:10.1038/nrc3151
Reference
PMID:21196257
  Authors
Overmeyer JH, Maltese WA
  Title
Death pathways triggered by activated Ras in cancer cells.
  Journal
Front Biosci (Landmark Ed) 16:1693-713 (2011)
DOI:10.2741/3814
Reference
PMID:16869784
  Authors
Rodriguez-Viciana P, Tetsu O, Oda K, Okada J, Rauen K, McCormick F
  Title
Cancer targets in the Ras pathway.
  Journal
Cold Spring Harb Symp Quant Biol 70:461-7 (2005)
DOI:10.1101/sqb.2005.70.044
Reference
PMID:14663478
  Authors
Cox AD, Der CJ
  Title
The dark side of Ras: regulation of apoptosis.
  Journal
Oncogene 22:8999-9006 (2003)
DOI:10.1038/sj.onc.1207111
Reference
PMID:18413813
  Authors
Braun BS, Shannon K
  Title
Targeting Ras in myeloid leukemias.
  Journal
Clin Cancer Res 14:2249-52 (2008)
DOI:10.1158/1078-0432.CCR-07-1005
Reference
PMID:20420946
  Authors
Pino MS, Chung DC
  Title
The chromosomal instability pathway in colon cancer.
  Journal
Gastroenterology 138:2059-72 (2010)
DOI:10.1053/j.gastro.2009.12.065
Reference
PMID:12217381
  Authors
Schrader JW, Schallhorn A, Grill B, Guo X
  Title
Activation of small GTPases of the Ras and Rho family by growth factors active on mast cells.
  Journal
Mol Immunol 38:1181-6 (2002)
DOI:10.1016/S0161-5890(02)00060-3
Reference
PMID:22189424
  Authors
Ahearn IM, Haigis K, Bar-Sagi D, Philips MR
  Title
Regulating the regulator: post-translational modification of RAS.
  Journal
Nat Rev Mol Cell Biol 13:39-51 (2012)
DOI:10.1038/nrm3255
Reference
PMID:11313946
  Authors
Ehrhardt GR, Korherr C, Wieler JS, Knaus M, Schrader JW
  Title
A novel potential effector of M-Ras and p21 Ras negatively regulates p21 Ras-mediated gene induction and cell growth.
  Journal
Oncogene 20:188-97 (2001)
DOI:10.1038/sj.onc.1204053
Reference
PMID:16966426
  Authors
Goldfinger LE, Ptak C, Jeffery ED, Shabanowitz J, Hunt DF, Ginsberg MH
  Title
RLIP76 (RalBP1) is an R-Ras effector that mediates adhesion-dependent Rac activation and cell migration.
  Journal
J Cell Biol 174:877-88 (2006)
DOI:10.1083/jcb.200603111
Reference
PMID:23506953
  Authors
Kortum RL, Rouquette-Jazdanian AK, Samelson LE
  Title
Ras and extracellular signal-regulated kinase signaling in thymocytes and T cells.
  Journal
Trends Immunol 34:259-68 (2013)
DOI:10.1016/j.it.2013.02.004
Reference
PMID:15572660
  Authors
Roberts DM, Anderson AL, Hidaka M, Swetenburg RL, Patterson C, Stanford WL, Bautch VL
  Title
A vascular gene trap screen defines RasGRP3 as an angiogenesis-regulated gene required for the endothelial response to phorbol esters.
  Journal
Mol Cell Biol 24:10515-28 (2004)
DOI:10.1128/MCB.24.24.10515-10528.2004
Reference
PMID:10712923
  Authors
Reuther GW, Der CJ
  Title
The Ras branch of small GTPases: Ras family members don't fall far from the tree.
  Journal
Curr Opin Cell Biol 12:157-65 (2000)
DOI:10.1016/S0955-0674(99)00071-X
Reference
PMID:21111786
  Authors
Fernandez-Medarde A, Santos E
  Title
The RasGrf family of mammalian guanine nucleotide exchange factors.
  Journal
Biochim Biophys Acta 1815:170-88 (2011)
DOI:10.1016/j.bbcan.2010.11.001
Reference
PMID:18437264
  Authors
Iwashita S, Song SY
  Title
RasGAPs: a crucial regulator of extracellular stimuli for homeostasis of cellular functions.
  Journal
Mol Biosyst 4:213-22 (2008)
DOI:10.1039/b716357f
Reference
PMID:15062121
  Authors
Ory S, Morrison DK
  Title
Signal transduction: implications for Ras-dependent ERK signaling.
  Journal
Curr Biol 14:R277-8 (2004)
DOI:10.1016/j.cub.2004.03.023
Reference
PMID:19091743
  Authors
Matheny SA, White MA
  Title
Signaling threshold regulation by the Ras effector IMP.
  Journal
J Biol Chem 284:11007-11 (2009)
DOI:10.1074/jbc.R800082200
Reference
PMID:20602996
  Authors
Lemmon MA, Schlessinger J
  Title
Cell signaling by receptor tyrosine kinases.
  Journal
Cell 141:1117-34 (2010)
DOI:10.1016/j.cell.2010.06.011
Reference
PMID:22367796
  Authors
Skaper SD
  Title
The neurotrophin family of neurotrophic factors: an overview.
  Journal
Methods Mol Biol 846:1-12 (2012)
DOI:10.1007/978-1-61779-536-7_1
Reference
PMID:34074494
  Authors
Apken LH, Oeckinghaus A
  Title
The RAL signaling network: Cancer and beyond.
  Journal
Int Rev Cell Mol Biol 361:21-105 (2021)
DOI:10.1016/bs.ircmb.2020.10.005
Related
pathway
ko04010  MAPK signaling pathway
ko04015  Rap1 signaling pathway
ko04020  Calcium signaling pathway
ko04144  Endocytosis
ko04151  PI3K-Akt signaling pathway
ko04660  T cell receptor signaling pathway
ko04720  Long-term potentiation
ko04810  Regulation of actin cytoskeleton

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