Ras signaling (Homo sapiens)

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ScaffoldApoptosisCell-cycle arrestEndocytosisCell-cell junctionsGrowth FactorsInactivePLA2G4BPLA2G16Ca2+RRASGRIN1PIP3GDPGRIN2AGRIN2BCa2+HTR7CSF1REGFREPHA2FGFR1FGFR3FGFR2FGFR4FLT1FLT3FLT4IGF1RINSRKDRKITMETNGFRNTRK1NTRK2PDGFRAPDGFRBTEKCALM1CALM2CALM3CALML3CALML4CALML5CALML6RASGRF1PRASGRF2PcAMPPRKACAPRKACBPRKACGGNB5GNB1GNB2GNB3GNG3GNG4GNG5GNG7GNG10GNG11GNGT1GNGT2GNG13GNG2GNG12GNB4GNG8PLCG1PLCG2DAGRASGRP1RASGRP2RASGRP3RASGRP4ZAP70LATIP3Ca2+GRB2SHC1SHC2SHC3SHC4GAB1GAB2PTPN11SOS1SOS2RRAS2MRASHRASKRASNRASGTPRRASRRAS2MRASHRASKRASNRASNF1RASA4BRASA4RASA3RASA1RASA2RASAL3RASAL1SYNGAP1RASAL2RASSF1RASSF5STK4STK4TIAM1RAC1RAC2RAC3PAK4BUB1B-PAK6PAK1PAK2PAK3PAK6PAK5RHOACytoskeleton organizationCell motilityAKT1AKT2AKT3CHUKPIKBKBIKBKGPNFKB1RELABADPBCL2L1FOXO4FASLGCell survival, growth, migrationCell cycle progressionTranscriptionAFDNSHOC2RAF1KSR1KSR2MAP2K1PMAP2K2PPPMAPK1PPMAPK3PPBRAPETS1ETS2ELK1Gene expressionPLA2G4EPLA2G4FPLA2G2DPLA2G4DPLA2G2EPLA2G2CPLA2G3PLA1APLA2G1BPLA2G2APLA2G4APLA2G5PLA2G2FPLA2G12APLA2G6PLA2G10PLA2G12BPLA2G4CJMJD7-PLA2G4BRAPGEF5RAP1ARAP1BRALGDSRGL1RGL2RALARALBMAPK8MAPK9MAPK10EXOC2TTBK1RELPLD1PLD2RALBP1RAC1RAC2RAC3CDC42Gene expressionPLCE1DAGPRKCAPRKCBPRKCGRIN1RALBP1ARF6RAC1Cell spreadingand migrationRAB5ARAB5BRAB5CABL1ABL2EndocytosisCytoskeletal remodelingIP3Ca2+ActivePIK3CAPIK3CBPIK3CDPIK3R1PIK3R2PIK3R3PIK3R3


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).

Pathway adapted from KEGG

When Ras is 'switched on' by incoming signals, it subsequently switches on other proteins, which ultimately turn on genes involved in cell growth, differentiation and survival. Mutations in ras genes can lead to the production of permanently activated Ras proteins. As a result, this can cause unintended and overactive signaling inside the cell, even in the absence of incoming signals.

Because these signals result in cell growth and division, overactive Ras signaling can ultimately lead to cancer. The 3 Ras genes in humans (HRas, KRas, and NRas) are the most common oncogenes in human cancer; mutations that permanently activate Ras are found in 20% to 25% of all human tumors and up to 90% in certain types of cancer. Wikipedia

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Ontology Terms

 

Bibliography

  1. Reuther GW, Der CJ; ''The Ras branch of small GTPases: Ras family members don't fall far from the tree.''; Curr Opin Cell Biol, 2000 PubMed Europe PMC Scholia
  2. ''KEGG Ras Signaling Pathway''; https://www.kegg.jp/dbget-bin/www_bget?pathway+hsa04014,

History

View all...
CompareRevisionActionTimeUserComment
127495view18:41, 11 October 2023Khanspersadded phosphosite for BAD
127494view18:38, 11 October 2023Khanspersfixed typo
127396view19:53, 29 September 2023Khanspersupdated phosphosites
119284view10:49, 23 June 2021Finterlyadded KEGG pathway info to publicationXref, removed duplicate info
116590view16:28, 8 May 2021EweitzModified title
107655view08:35, 25 October 2019DeSlConverted MIM-conversions to Arrow between GeneProducts/Proteins.
106500view21:45, 4 September 2019KhanspersModified description
105681view23:24, 12 August 2019KhanspersModified description
105675view21:57, 12 August 2019Khanspersupdated layout
105441view04:53, 8 August 2019KhanspersModified description
105368view15:05, 5 August 2019DeSlUpdating last title field to show reference to Kegg PW correctly.
105367view15:00, 5 August 2019DeSlUpdating PW ref to see title.
105366view14:58, 5 August 2019DeSlAdded lit. ref for Ras -> RalGDS stimulation.
105343view00:32, 2 August 2019KhanspersAdded KEGG reference
105342view00:31, 2 August 2019KhanspersModified description
105341view00:14, 2 August 2019Khanspersnew layout
105340view23:52, 1 August 2019Khanspersupdated layout - work in progress
96928view17:53, 20 April 2018Khanspersremoved duplicated node
96927view17:21, 20 April 2018Khanspersrefined layout and added phosphosites
96441view08:03, 15 March 2018EgonwReplaced secondary ChEBI identifiers with primary identifiers.
96363view22:23, 9 March 2018KhanspersModified description
96274view17:30, 4 March 2018KhanspersOntology Term : 'growth factor signaling pathway' added !
96273view17:29, 4 March 2018KhanspersOntology Term : 'Ras superfamily mediated signaling pathway' added !
96238view06:54, 2 March 2018KhanspersModified description
96237view06:52, 2 March 2018KhanspersModified description
96236view06:51, 2 March 2018KhanspersNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ABL1GeneProductENSG00000097007 (Ensembl)
ABL2GeneProductENSG00000143322 (Ensembl)
AFDNGeneProduct4301 (Entrez Gene)
AKT1GeneProductENSG00000142208 (Ensembl)
AKT2GeneProductENSG00000105221 (Ensembl)
AKT3GeneProductENSG00000117020 (Ensembl)
ARF6GeneProductENSG00000165527 (Ensembl)
BADGeneProductENSG00000002330 (Ensembl)
BCL2L1GeneProductENSG00000171552 (Ensembl)
BRAPGeneProductENSG00000089234 (Ensembl)
BUB1B-PAK6GeneProductENSG00000259288 (Ensembl)
CALM1GeneProductENSG00000198668 (Ensembl)
CALM2GeneProductENSG00000143933 (Ensembl)
CALM3GeneProductENSG00000160014 (Ensembl)
CALML3GeneProductENSG00000178363 (Ensembl)
CALML4GeneProductENSG00000129007 (Ensembl)
CALML5GeneProductENSG00000178372 (Ensembl)
CALML6GeneProductENSG00000169885 (Ensembl)
CDC42GeneProductENSG00000070831 (Ensembl)
CHUKGeneProductENSG00000213341 (Ensembl)
CSF1RGeneProductENSG00000182578 (Ensembl)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
DAGMetaboliteCHEBI:18035 (ChEBI)
EGFRGeneProductENSG00000146648 (Ensembl)
ELK1GeneProductENSG00000126767 (Ensembl)
EPHA2GeneProductENSG00000142627 (Ensembl)
ETS1GeneProductENSG00000134954 (Ensembl)
ETS2GeneProductENSG00000157557 (Ensembl)
EXOC2GeneProductENSG00000112685 (Ensembl)
FASLGGeneProductENSG00000117560 (Ensembl)
FGFR1GeneProductENSG00000077782 (Ensembl)
FGFR2GeneProductENSG00000066468 (Ensembl)
FGFR3GeneProductENSG00000068078 (Ensembl)
FGFR4GeneProductENSG00000160867 (Ensembl)
FLT1GeneProductENSG00000102755 (Ensembl)
FLT3GeneProductENSG00000122025 (Ensembl)
FLT4GeneProductENSG00000037280 (Ensembl)
FOXO4GeneProductENSG00000184481 (Ensembl)
GAB1GeneProductENSG00000109458 (Ensembl)
GAB2GeneProductENSG00000033327 (Ensembl)
GDPMetaboliteCHEBI:17552 (ChEBI)
GNB1GeneProductENSG00000078369 (Ensembl)
GNB2GeneProductENSG00000172354 (Ensembl)
GNB3GeneProductENSG00000111664 (Ensembl)
GNB4GeneProductENSG00000114450 (Ensembl)
GNB5GeneProductENSG00000069966 (Ensembl)
GNG10GeneProductENSG00000242616 (Ensembl)
GNG11GeneProductENSG00000127920 (Ensembl)
GNG12GeneProductENSG00000172380 (Ensembl)
GNG13GeneProductENSG00000127588 (Ensembl)
GNG2GeneProductENSG00000186469 (Ensembl)
GNG3GeneProductENSG00000162188 (Ensembl)
GNG4GeneProductENSG00000168243 (Ensembl)
GNG5GeneProductENSG00000174021 (Ensembl)
GNG7GeneProductENSG00000176533 (Ensembl)
GNG8GeneProductENSG00000167414 (Ensembl)
GNGT1GeneProductENSG00000127928 (Ensembl)
GNGT2GeneProductENSG00000167083 (Ensembl)
GRB2GeneProductENSG00000177885 (Ensembl)
GRIN1GeneProductENSG00000176884 (Ensembl)
GRIN2AGeneProductENSG00000183454 (Ensembl)
GRIN2BGeneProductENSG00000273079 (Ensembl)
GTPMetaboliteCHEBI:15996 (ChEBI)
HRASGeneProductENSG00000174775 (Ensembl)
HTR7GeneProductENSG00000148680 (Ensembl)
IGF1RGeneProductENSG00000140443 (Ensembl)
IKBKBGeneProductENSG00000104365 (Ensembl)
IKBKGGeneProductENSG00000269335 (Ensembl)
INSRGeneProductENSG00000171105 (Ensembl)
IP3MetaboliteCHEBI:16595 (ChEBI)
JMJD7-PLA2G4BGeneProductENSG00000168970 (Ensembl)
KDRGeneProductENSG00000128052 (Ensembl)
KITGeneProductENSG00000157404 (Ensembl)
KRASGeneProductENSG00000133703 (Ensembl)
KSR1GeneProductENSG00000141068 (Ensembl)
KSR2GeneProductENSG00000171435 (Ensembl)
LATGeneProduct27040 (Entrez Gene)
MAP2K1GeneProductENSG00000169032 (Ensembl)
MAP2K2GeneProductENSG00000126934 (Ensembl)
MAPK10GeneProductENSG00000109339 (Ensembl)
MAPK1GeneProductENSG00000100030 (Ensembl)
MAPK3GeneProductENSG00000102882 (Ensembl)
MAPK8GeneProductENSG00000107643 (Ensembl)
MAPK9GeneProductENSG00000050748 (Ensembl)
METGeneProduct4233 (Entrez Gene)
MRASGeneProductENSG00000158186 (Ensembl)
NF1GeneProduct4763 (Entrez Gene)
NFKB1GeneProductENSG00000109320 (Ensembl)
NGFRGeneProductENSG00000064300 (Ensembl)
NRASGeneProductENSG00000213281 (Ensembl)
NTRK1GeneProductENSG00000198400 (Ensembl)
NTRK2GeneProductENSG00000148053 (Ensembl)
PAK1GeneProductENSG00000149269 (Ensembl)
PAK2GeneProductENSG00000180370 (Ensembl)
PAK3GeneProductENSG00000077264 (Ensembl)
PAK4GeneProductENSG00000130669 (Ensembl)
PAK5GeneProductENSG00000101349 (Ensembl)
PAK6GeneProductENSG00000137843 (Ensembl)
PDGFRAGeneProductENSG00000134853 (Ensembl)
PDGFRBGeneProductENSG00000113721 (Ensembl)
PIK3CAGeneProductENSG00000121879 (Ensembl)
PIK3CBGeneProductENSG00000051382 (Ensembl)
PIK3CDGeneProductENSG00000171608 (Ensembl)
PIK3R1GeneProductENSG00000145675 (Ensembl)
PIK3R2GeneProductENSG00000105647 (Ensembl)
PIK3R3GeneProductENSG00000117461 (Ensembl)
PIP3MetaboliteCHEBI:16618 (ChEBI)
PLA1AGeneProductENSG00000144837 (Ensembl)
PLA2G10GeneProductENSG00000069764 (Ensembl)
PLA2G12AGeneProductENSG00000123739 (Ensembl)
PLA2G12BGeneProductENSG00000138308 (Ensembl)
PLA2G16GeneProductENSG00000176485 (Ensembl)
PLA2G1BGeneProductENSG00000170890 (Ensembl)
PLA2G2AGeneProductENSG00000188257 (Ensembl)
PLA2G2CGeneProductENSG00000187980 (Ensembl)
PLA2G2DGeneProductENSG00000117215 (Ensembl)
PLA2G2EGeneProductENSG00000188784 (Ensembl)
PLA2G2FGeneProductENSG00000158786 (Ensembl)
PLA2G3GeneProductENSG00000100078 (Ensembl)
PLA2G4AGeneProductENSG00000116711 (Ensembl)
PLA2G4BGeneProductENSG00000243708 (Ensembl)
PLA2G4CGeneProductENSG00000105499 (Ensembl)
PLA2G4DGeneProductENSG00000159337 (Ensembl)
PLA2G4EGeneProductENSG00000188089 (Ensembl)
PLA2G4FGeneProductENSG00000168907 (Ensembl)
PLA2G5GeneProductENSG00000127472 (Ensembl)
PLA2G6GeneProductENSG00000184381 (Ensembl)
PLCE1GeneProductENSG00000138193 (Ensembl)
PLCG1GeneProductENSG00000124181 (Ensembl)
PLCG2GeneProductENSG00000197943 (Ensembl)
PLD1GeneProductENSG00000075651 (Ensembl)
PLD2GeneProductENSG00000129219 (Ensembl)
PRKACAGeneProductENSG00000072062 (Ensembl)
PRKACBGeneProductENSG00000142875 (Ensembl)
PRKACGGeneProductENSG00000165059 (Ensembl)
PRKCAGeneProductENSG00000154229 (Ensembl)
PRKCBGeneProductENSG00000166501 (Ensembl)
PRKCGGeneProductENSG00000126583 (Ensembl)
PTPN11GeneProductENSG00000179295 (Ensembl)
RAB5AGeneProductENSG00000144566 (Ensembl)
RAB5BGeneProductENSG00000111540 (Ensembl)
RAB5CGeneProductENSG00000108774 (Ensembl)
RAC1GeneProductENSG00000136238 (Ensembl)
RAC2GeneProductENSG00000128340 (Ensembl)
RAC3GeneProductENSG00000169750 (Ensembl)
RAF1GeneProductENSG00000132155 (Ensembl)
RALAGeneProductENSG00000006451 (Ensembl)
RALBGeneProductENSG00000144118 (Ensembl)
RALBP1GeneProductENSG00000017797 (Ensembl)
RALGDSGeneProductENSG00000160271 (Ensembl)
RAP1AGeneProductENSG00000116473 (Ensembl)
RAP1BGeneProductENSG00000127314 (Ensembl)
RAPGEF5GeneProductENSG00000136237 (Ensembl)
RASA1GeneProductENSG00000145715 (Ensembl)
RASA2GeneProductENSG00000155903 (Ensembl)
RASA3GeneProductENSG00000185989 (Ensembl)
RASA4BGeneProductENSG00000170667 (Ensembl)
RASA4GeneProductENSG00000105808 (Ensembl)
RASAL1GeneProductENSG00000111344 (Ensembl)
RASAL2GeneProductENSG00000075391 (Ensembl)
RASAL3GeneProductENSG00000105122 (Ensembl)
RASGRF1GeneProductENSG00000058335 (Ensembl)
RASGRF2GeneProductENSG00000113319 (Ensembl)
RASGRP1GeneProductENSG00000172575 (Ensembl)
RASGRP2GeneProductENSG00000068831 (Ensembl)
RASGRP3GeneProductENSG00000152689 (Ensembl)
RASGRP4GeneProductENSG00000171777 (Ensembl)
RASSF1GeneProductENSG00000068028 (Ensembl)
RASSF5GeneProductENSG00000266094 (Ensembl)
RELGeneProduct5966 (Entrez Gene)
RELAGeneProduct5970 (Entrez Gene)
RGL1GeneProductENSG00000143344 (Ensembl)
RGL2GeneProductENSG00000237441 (Ensembl)
RHOAGeneProductENSG00000067560 (Ensembl)
RIN1GeneProductENSG00000174791 (Ensembl)
RRAS2GeneProductENSG00000133818 (Ensembl)
RRASGeneProductENSG00000126458 (Ensembl)
SHC1GeneProductENSG00000160691 (Ensembl)
SHC2GeneProductENSG00000129946 (Ensembl)
SHC3GeneProductENSG00000148082 (Ensembl)
SHC4GeneProductENSG00000185634 (Ensembl)
SHOC2GeneProductENSG00000108061 (Ensembl)
SOS1GeneProductENSG00000115904 (Ensembl)
SOS2GeneProductENSG00000100485 (Ensembl)
STK4GeneProductENSG00000101109 (Ensembl)
SYNGAP1GeneProductENSG00000197283 (Ensembl)
TEKGeneProductENSG00000120156 (Ensembl)
TIAM1GeneProductENSG00000156299 (Ensembl)
TTBK1GeneProductENSG00000146216 (Ensembl)
ZAP70GeneProductENSG00000115085 (Ensembl)
cAMPMetaboliteCHEBI:17489 (ChEBI)

Annotated Interactions

No annotated interactions

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