Ras Signaling (Homo sapiens)

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ScaffoldInactiveGrowth FactorsEndocytosisApoptosisCell-cycle arrestCell-cell junctionsGDPGRIN1PLA2G4BRRASPLA2G16Ca2+PIP3GRIN2AGRIN2BCa2+HTR7CSF1REGFREPHA2FGFR1FGFR3FGFR2FGFR4FLT1FLT3FLT4IGF1RINSRKDRKITMETNGFRNTRK1NTRK2PDGFRAPDGFRBTEKCALM1CALM2CALM3CALML3CALML4CALML5CALML6RASGRF1PRASGRF2PcAMPPRKACAPRKACBPRKACGGNB5GNB1GNB2GNB3GNG3GNG4GNG5GNG7GNG10GNG11GNGT1GNGT2GNG13GNG2GNG12GNB4GNG8PLCG1PLCG2DAGRASGRP1RASGRP2RASGRP3RASGRP4ZAP70LATIP3Ca2+GRB2SHC1SHC2SHC3SHC4GAB1GAB2PTPN11SOS1SOS2RRAS2MRASHRASKRASNRASGTPRRASRRAS2MRASHRASKRASNRASNF1RASA4BRASA4RASA3RASA1RASA2RASAL3RASAL1SYNGAP1RASAL2RASSF1RASSF5STK4STK4TIAM1RAC1RAC2RAC3PAK4BUB1B-PAK6PAK1PAK2PAK3PAK6PAK5RHOACytoskeleton organizationCell motilityAKT1AKT2AKT3CHUKPIKBKBIKBKGPNFKB1RELABADPBCL2L1FOXO4FASLGCell survival, growth, migrationCell cycle progressionTranscriptionAFDNSHOC2RAF1KSR1KSR2MAP2K1PPMAP2K2PPMAPK1MAPK3PPPPBRAPETS1ETS2ELK1Gene expressionPLA2G4EPLA2G4FPLA2G2DPLA2G4DPLA2G2EPLA2G2CPLA2G3PLA1APLA2G1BPLA2G2APLA2G4APLA2G5PLA2G2FPLA2G12APLA2G6PLA2G10PLA2G12BPLA2G4CJMJD7-PLA2G4BRAPGEF5RAP1ARAP1BRALGDSRGL1RGL2RALARALBMAPK8MAPK9MAPK10EXOC2TTBK1RELPLD1PLD2RALBP1RAC1RAC2RAC3CDC42Gene expressionPLCE1DAGPRKCAPRKCBPRKCGRIN1RALBP1ARF6RAC1Cell spreadingand migrationRAB5ARAB5BRAB5CABL1ABL2EndocytosisCytoskeletal remodelingIP3Ca2+ActivePIK3CAPIK3CBPIK3CDPIK3R1PIK3R2PIK3R3


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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Bibliography

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History

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CompareRevisionActionTimeUserComment
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

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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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