KEGG   PATHWAY: ko04014Help
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
09130 Environmental Information Processing; 09132 Signal transduction
BRITE hierarchy
Pathway map
ko04014  Ras signaling pathway
ko04014

Ortholog table
Disease
H00505  FGFR3-related short limb skeletal dysplasia
H01437  Neurofibromatosis type 1
H01738  Noonan syndrome
H01747  Costello syndrome
H01984  Leopard syndrome
H02068  Hypochondroplasia
H02069  SADDAN
Other DBs
BSID: 878044
GO: 0032318
Orthology
K04357  epidermal growth factor
K08774  transforming growth factor, alpha
K18496  fibroblast growth factor 1
K18497  fibroblast growth factor 2
K04358  fibroblast growth factor
K22603  fibroblast growth factor 19
K22429  fibroblast growth factor 21
K22428  fibroblast growth factor 23
K05451  nerve growth factor, alpha
K02582  nerve growth factor, beta
K04355  brain-derived neurotrophic factor
K04356  neurotrophin 3
K12457  neurotrophin 4
K04526  insulin
K05459  insulin-like growth factor 1
K13769  insulin-like growth factor 2
K04359  platelet-derived growth factor subunit A
K17386  platelet-derived growth factor subunit B
K05450  platelet derived growth factor C/D
K05453  macrophage colony-stimulating factor 1
K05461  KIT ligand
K05454  fms-related tyrosine kinase 3 ligand
K05448  vascular endothelial growth factor A
K16858  vascular endothelial growth factor B
K16859  placenta growth factor
K05449  vascular endothelial growth factor C/D
K05460  hepatocyte growth factor
K05465  angiopoietin 1
K05466  angiopoietin 2
K05467  angiopoietin 4
K05462  ephrin-A
K04361  epidermal growth factor receptor [EC:2.7.10.1]
K04362  fibroblast growth factor receptor 1 [EC:2.7.10.1]
K05093  fibroblast growth factor receptor 2 [EC:2.7.10.1]
K05094  fibroblast growth factor receptor 3 [EC:2.7.10.1]
K05095  fibroblast growth factor receptor 4 [EC:2.7.10.1]
K02583  tumor necrosis factor receptor superfamily member 16
K03176  neurotrophic tyrosine kinase receptor type 1 [EC:2.7.10.1]
K04360  neurotrophic tyrosine kinase receptor type 2 [EC:2.7.10.1]
K04527  insulin receptor [EC:2.7.10.1]
K05087  insulin-like growth factor 1 receptor [EC:2.7.10.1]
K04363  platelet-derived growth factor receptor alpha [EC:2.7.10.1]
K05089  platelet-derived growth factor receptor beta [EC:2.7.10.1]
K05090  macrophage colony-stimulating factor 1 receptor [EC:2.7.10.1]
K05091  proto-oncogene tyrosine-protein kinase Kit [EC:2.7.10.1]
K05092  fms-related tyrosine kinase 3 [EC:2.7.10.1]
K05096  FMS-like tyrosine kinase 1 [EC:2.7.10.1]
K05097  FMS-like tyrosine kinase 4 [EC:2.7.10.1]
K05098  kinase insert domain protein receptor [EC:2.7.10.1]
K05099  proto-oncogene tyrosine-protein kinase Met [EC:2.7.10.1]
K05121  endothelial-specific receptor tyrosine kinase [EC:2.7.10.1]
K05103  Eph receptor A2 [EC:2.7.10.1]
K04364  growth factor receptor-binding protein 2
K09593  GRB2-associated-binding protein 1
K08091  growth factor receptor bound protein 2-associated protein 2
K06279  SHC-transforming protein 1
K17447  SHC-transforming protein 2
K17448  SHC-transforming protein 3
K17449  SHC-transforming protein 4
K07293  tyrosine-protein phosphatase non-receptor type 11 [EC:3.1.3.48]
K03099  son of sevenless
K01116  phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11]
K05859  phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11]
K04350  RAS guanyl-releasing protein 1
K12361  RAS guanyl-releasing protein 2
K12362  RAS guanyl-releasing protein 3
K12363  RAS guanyl-releasing protein 4
K10784  T cell receptor alpha chain V region
K10785  T-cell receptor beta chain V region
K07360  tyrosine-protein kinase ZAP-70 [EC:2.7.10.2]
K07362  linker for activation of T cells
K04163  5-hydroxytryptamine receptor 7
K04536  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04537  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
K07825  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
K04538  guanine nucleotide-binding protein subunit beta-4
K04539  guanine nucleotide-binding protein subunit beta-5
K07826  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
K04540  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
K04541  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
K04542  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
K04543  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04544  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
K04545  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
K04546  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
K04347  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04547  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04548  guanine nucleotide-binding protein G(T) subunit gamma-T1
K04549  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
K04345  protein kinase A [EC:2.7.11.11]
K04349  Ras-specific guanine nucleotide-releasing factor 1
K12326  Ras-specific guanine nucleotide-releasing factor 2
K05208  glutamate receptor ionotropic, NMDA 1
K05209  glutamate receptor ionotropic, NMDA 2A
K05210  glutamate receptor ionotropic, NMDA 2B
K02183  calmodulin
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K07831  Ras-related protein M-Ras
K07829  Ras-related protein R-Ras
K07830  Ras-related protein R-Ras2
K08052  neurofibromin 1
K04352  Ras GTPase-activating protein 1
K08053  Ras GTPase-activating protein 2
K12380  Ras GTPase-activating protein 3
K17630  Ras GTPase-activating protein 4
K17631  Ras/Rap GTPase-activating protein SynGAP
K17632  RAS protein activator-like 1
K17633  RAS protein activator-like 2
K17634  RAS protein activator-like 3
K09850  Ras association domain-containing protein 1
K08015  Ras association domain-containing protein 5
K04411  serine/threonine kinase 4
K05731  T-lymphoma invasion and metastasis-inducing protein 1
K04392  Ras-related C3 botulinum toxin substrate 1
K07860  Ras-related C3 botulinum toxin substrate 2
K07861  Ras-related C3 botulinum toxin substrate 3
K04409  p21-activated kinase 1 [EC:2.7.11.1]
K04410  p21-activated kinase 2 [EC:2.7.11.1]
K05733  p21-activated kinase 3 [EC:2.7.11.1]
K05734  p21-activated kinase 4 [EC:2.7.11.1]
K05736  p21-activated kinase 5 [EC:2.7.11.1]
K05735  p21-activated kinase 6 [EC:2.7.11.1]
K04513  Ras homolog gene family, member A
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04456  RAC serine/threonine-protein kinase [EC:2.7.11.1]
K07210  inhibitor of nuclear factor kappa-B kinase subunit gamma
K04467  inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K07209  inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K02580  nuclear factor NF-kappa-B p105 subunit
K04735  transcription factor p65
K02158  Bcl-2-antagonist of cell death
K04570  Bcl-2-like 1 (apoptosis regulator Bcl-X)
K12358  forkhead box protein O4
K04389  tumor necrosis factor ligand superfamily member 6
K05702  afadin
K19613  leucine-rich repeat protein SHOC2
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K13618  phospholipase A1 member A [EC:3.1.1.-]
K01047  secretory phospholipase A2 [EC:3.1.1.4]
K16342  cytosolic phospholipase A2 [EC:3.1.1.4]
K16343  calcium-independent phospholipase A2 [EC:3.1.1.4]
K16817  HRAS-like suppressor 3 [EC:3.1.1.4 3.1.1.32]
K04375  ETS domain-containing protein Elk-1
K02678  C-ets-1
K21932  C-ets-2
K10632  BRCA1-associated protein [EC:2.3.2.27]
K14958  kinase suppressor of Ras 1
K18529  kinase suppressor of Ras 2 [EC:2.7.11.1]
K08019  Rap guanine nucleotide exchange factor 5
K04353  Ras-related protein Rap-1A
K07836  Ras-related protein Rap-1B
K08732  ral guanine nucleotide dissociation stimulator
K17635  ral guanine nucleotide dissociation stimulator-like 1
K17636  ral guanine nucleotide dissociation stimulator-like 2
K07834  Ras-related protein Ral-A
K07835  Ras-related protein Ral-B
K04440  mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K17637  exocyst complex component 2
K05410  TANK-binding kinase 1 [EC:2.7.11.10]
K09254  c-Rel proto-oncogene protein
K01115  phospholipase D1/2 [EC:3.1.4.4]
K08773  RalA-binding protein 1
K04393  cell division control protein 42
K05860  phosphatidylinositol phospholipase C, epsilon [EC:3.1.4.11]
K02677  classical protein kinase C alpha type [EC:2.7.11.13]
K19662  classical protein kinase C beta type [EC:2.7.11.13]
K19663  classical protein kinase C gamma type [EC:2.7.11.13]
K17638  Ras and Rab interactor 1
K06619  abelson tyrosine-protein kinase 1 [EC:2.7.10.2]
K08887  abelson tyrosine-protein kinase 2 [EC:2.7.10.2]
K07887  Ras-related protein Rab-5A
K07888  Ras-related protein Rab-5B
K07889  Ras-related protein Rab-5C
K07941  ADP-ribosylation factor 6
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
  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
  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
  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
  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
  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
  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
  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
  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
  Authors
Overmeyer JH, Maltese WA
  Title
Death pathways triggered by activated Ras in cancer cells.
  Journal
Front Biosci (Landmark Ed) 16:1693-713 (2011)
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
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