Ras signaling (WP4223)

Homo sapiens

Ras proteins are small GTPases and are involved in transmitting signals within cells. In this way, Ras signaling controls many downstream processes, including cell proliferation, survival, growth, migration and differentiation. Ras proteins exists in two states, inactive while bound to GDP and active while bound to GTP. The exchange of GTP for GDP on RAS proteins is regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Activated RAS regulates cellular functions through a set of effector molecules, including Raf, phosphatidylinositol 3-kinase (PI3K) and Ral guanine nucleotide-dissociation stimulator (RALGDS). Mutations in Ras genes can lead to the production of permanently activated Ras proteins. 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. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP4223 CPTAC Assay Portal]

Authors

Kristina Hanspers , Egon Willighagen , Denise Slenter , Eric Weitz , and Finterly Hu

Activity

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Organisms

Homo sapiens

Communities

CPTAC PancCanNet

Annotations

Pathway Ontology

growth factor signaling pathway Ras superfamily mediated signaling pathway

Participants

Label Type Compact URI Comment
GDP Metabolite chebi:17552
Ca2+ Metabolite chebi:29108
PIP3 Metabolite chebi:16618
Ca2+ Metabolite chebi:29108
cAMP Metabolite chebi:17489
DAG Metabolite chebi:18035
IP3 Metabolite chebi:16595
Ca2+ Metabolite chebi:29108
GTP Metabolite chebi:15996
DAG Metabolite chebi:18035
IP3 Metabolite chebi:16595
Ca2+ Metabolite chebi:29108
PLA2G4B GeneProduct ensembl:ENSG00000243708
GRIN1 GeneProduct ensembl:ENSG00000176884
PLA2G16 GeneProduct ensembl:ENSG00000176485
RRAS GeneProduct ensembl:ENSG00000126458
GRIN2A GeneProduct ensembl:ENSG00000183454
GRIN2B GeneProduct ensembl:ENSG00000273079
HTR7 GeneProduct ensembl:ENSG00000148680
CSF1R GeneProduct ensembl:ENSG00000182578
EGFR GeneProduct ensembl:ENSG00000146648
EPHA2 GeneProduct ensembl:ENSG00000142627
FGFR1 GeneProduct ensembl:ENSG00000077782
FGFR3 GeneProduct ensembl:ENSG00000068078
FGFR2 GeneProduct ensembl:ENSG00000066468
FGFR4 GeneProduct ensembl:ENSG00000160867
FLT1 GeneProduct ensembl:ENSG00000102755
FLT3 GeneProduct ensembl:ENSG00000122025
FLT4 GeneProduct ensembl:ENSG00000037280
IGF1R GeneProduct ensembl:ENSG00000140443
INSR GeneProduct ensembl:ENSG00000171105
KDR GeneProduct ensembl:ENSG00000128052
KIT GeneProduct ensembl:ENSG00000157404
MET GeneProduct ncbigene:4233
NGFR GeneProduct ensembl:ENSG00000064300
NTRK1 GeneProduct ensembl:ENSG00000198400
NTRK2 GeneProduct ensembl:ENSG00000148053
PDGFRA GeneProduct ensembl:ENSG00000134853
PDGFRB GeneProduct ensembl:ENSG00000113721
TEK GeneProduct ensembl:ENSG00000120156
CALM1 GeneProduct ensembl:ENSG00000198668
CALM2 GeneProduct ensembl:ENSG00000143933
CALM3 GeneProduct ensembl:ENSG00000160014
CALML3 GeneProduct ensembl:ENSG00000178363
CALML4 GeneProduct ensembl:ENSG00000129007
CALML5 GeneProduct ensembl:ENSG00000178372
CALML6 GeneProduct ensembl:ENSG00000169885
RASGRF1 GeneProduct ensembl:ENSG00000058335
RASGRF2 GeneProduct ensembl:ENSG00000113319
PRKACA GeneProduct ensembl:ENSG00000072062
PRKACB GeneProduct ensembl:ENSG00000142875
PRKACG GeneProduct ensembl:ENSG00000165059
GNB5 GeneProduct ensembl:ENSG00000069966
GNB1 GeneProduct ensembl:ENSG00000078369
GNB2 GeneProduct ensembl:ENSG00000172354
GNB3 GeneProduct ensembl:ENSG00000111664
GNG3 GeneProduct ensembl:ENSG00000162188
GNG4 GeneProduct ensembl:ENSG00000168243
GNG5 GeneProduct ensembl:ENSG00000174021
GNG7 GeneProduct ensembl:ENSG00000176533
GNG10 GeneProduct ensembl:ENSG00000242616
GNG11 GeneProduct ensembl:ENSG00000127920
GNGT1 GeneProduct ensembl:ENSG00000127928
GNGT2 GeneProduct ensembl:ENSG00000167083
GNG13 GeneProduct ensembl:ENSG00000127588
GNG2 GeneProduct ensembl:ENSG00000186469
GNG12 GeneProduct ensembl:ENSG00000172380
GNB4 GeneProduct ensembl:ENSG00000114450
GNG8 GeneProduct ensembl:ENSG00000167414
PLCG1 GeneProduct ensembl:ENSG00000124181
PLCG2 GeneProduct ensembl:ENSG00000197943
RASGRP1 GeneProduct ensembl:ENSG00000172575
RASGRP2 GeneProduct ensembl:ENSG00000068831
RASGRP3 GeneProduct ensembl:ENSG00000152689
RASGRP4 GeneProduct ensembl:ENSG00000171777
ZAP70 GeneProduct ensembl:ENSG00000115085
LAT GeneProduct ncbigene:27040
GRB2 GeneProduct ensembl:ENSG00000177885
SHC1 GeneProduct ensembl:ENSG00000160691
SHC2 GeneProduct ensembl:ENSG00000129946
SHC3 GeneProduct ensembl:ENSG00000148082
SHC4 GeneProduct ensembl:ENSG00000185634
GAB1 GeneProduct ensembl:ENSG00000109458
GAB2 GeneProduct ensembl:ENSG00000033327
PTPN11 GeneProduct ensembl:ENSG00000179295
SOS1 GeneProduct ensembl:ENSG00000115904
SOS2 GeneProduct ensembl:ENSG00000100485
RRAS2 GeneProduct ensembl:ENSG00000133818
MRAS GeneProduct ensembl:ENSG00000158186
HRAS GeneProduct ensembl:ENSG00000174775
KRAS GeneProduct ensembl:ENSG00000133703
NRAS GeneProduct ensembl:ENSG00000213281
RRAS GeneProduct ensembl:ENSG00000126458
RRAS2 GeneProduct ensembl:ENSG00000133818
MRAS GeneProduct ensembl:ENSG00000158186
HRAS GeneProduct ensembl:ENSG00000174775
KRAS GeneProduct ensembl:ENSG00000133703
NRAS GeneProduct ensembl:ENSG00000213281
NF1 GeneProduct ncbigene:4763
RASA4B GeneProduct ensembl:ENSG00000170667
RASA4 GeneProduct ensembl:ENSG00000105808
RASA3 GeneProduct ensembl:ENSG00000185989
RASA1 GeneProduct ensembl:ENSG00000145715
RASA2 GeneProduct ensembl:ENSG00000155903
RASAL3 GeneProduct ensembl:ENSG00000105122
RASAL1 GeneProduct ensembl:ENSG00000111344
SYNGAP1 GeneProduct ensembl:ENSG00000197283
RASAL2 GeneProduct ensembl:ENSG00000075391
RASSF1 GeneProduct ensembl:ENSG00000068028
RASSF5 GeneProduct ensembl:ENSG00000266094
STK4 GeneProduct ensembl:ENSG00000101109
STK4 GeneProduct ensembl:ENSG00000101109
TIAM1 GeneProduct ensembl:ENSG00000156299
RAC1 GeneProduct ensembl:ENSG00000136238
RAC2 GeneProduct ensembl:ENSG00000128340
RAC3 GeneProduct ensembl:ENSG00000169750
PAK4 GeneProduct ensembl:ENSG00000130669
BUB1B-PAK6 GeneProduct ensembl:ENSG00000259288
PAK1 GeneProduct ensembl:ENSG00000149269
PAK2 GeneProduct ensembl:ENSG00000180370
PAK3 GeneProduct ensembl:ENSG00000077264
PAK6 GeneProduct ensembl:ENSG00000137843
PAK5 GeneProduct ensembl:ENSG00000101349
RHOA GeneProduct ensembl:ENSG00000067560
AKT1 GeneProduct ensembl:ENSG00000142208
AKT2 GeneProduct ensembl:ENSG00000105221
AKT3 GeneProduct ensembl:ENSG00000117020
CHUK GeneProduct ensembl:ENSG00000213341
IKBKB GeneProduct ensembl:ENSG00000104365
IKBKG GeneProduct ensembl:ENSG00000269335
NFKB1 GeneProduct ensembl:ENSG00000109320
RELA GeneProduct ncbigene:5970
BAD GeneProduct ensembl:ENSG00000002330
BCL2L1 GeneProduct ensembl:ENSG00000171552
FOXO4 GeneProduct ensembl:ENSG00000184481
FASLG GeneProduct ensembl:ENSG00000117560
AFDN GeneProduct ncbigene:4301
SHOC2 GeneProduct ensembl:ENSG00000108061
RAF1 GeneProduct ensembl:ENSG00000132155
KSR1 GeneProduct ensembl:ENSG00000141068
KSR2 GeneProduct ensembl:ENSG00000171435
MAP2K1 GeneProduct ensembl:ENSG00000169032
MAP2K2 GeneProduct ensembl:ENSG00000126934
MAPK1 GeneProduct ensembl:ENSG00000100030
MAPK3 GeneProduct ensembl:ENSG00000102882
BRAP GeneProduct ensembl:ENSG00000089234
ETS1 GeneProduct ensembl:ENSG00000134954
ETS2 GeneProduct ensembl:ENSG00000157557
ELK1 GeneProduct ensembl:ENSG00000126767
PLA2G4E GeneProduct ensembl:ENSG00000188089
PLA2G4F GeneProduct ensembl:ENSG00000168907
PLA2G2D GeneProduct ensembl:ENSG00000117215
PLA2G4D GeneProduct ensembl:ENSG00000159337
PLA2G2E GeneProduct ensembl:ENSG00000188784
PLA2G2C GeneProduct ensembl:ENSG00000187980
PLA2G3 GeneProduct ensembl:ENSG00000100078
PLA1A GeneProduct ensembl:ENSG00000144837
PLA2G1B GeneProduct ensembl:ENSG00000170890
PLA2G2A GeneProduct ensembl:ENSG00000188257
PLA2G4A GeneProduct ensembl:ENSG00000116711
PLA2G5 GeneProduct ensembl:ENSG00000127472
PLA2G2F GeneProduct ensembl:ENSG00000158786
PLA2G12A GeneProduct ensembl:ENSG00000123739
PLA2G6 GeneProduct ensembl:ENSG00000184381
PLA2G10 GeneProduct ensembl:ENSG00000069764
PLA2G12B GeneProduct ensembl:ENSG00000138308
PLA2G4C GeneProduct ensembl:ENSG00000105499
JMJD7-PLA2G4B GeneProduct ensembl:ENSG00000168970
RAPGEF5 GeneProduct ensembl:ENSG00000136237
RAP1A GeneProduct ensembl:ENSG00000116473
RAP1B GeneProduct ensembl:ENSG00000127314
RALGDS GeneProduct ensembl:ENSG00000160271
RGL1 GeneProduct ensembl:ENSG00000143344
RGL2 GeneProduct ensembl:ENSG00000237441
RALA GeneProduct ensembl:ENSG00000006451
RALB GeneProduct ensembl:ENSG00000144118
MAPK8 GeneProduct ensembl:ENSG00000107643
MAPK9 GeneProduct ensembl:ENSG00000050748
MAPK10 GeneProduct ensembl:ENSG00000109339
EXOC2 GeneProduct ensembl:ENSG00000112685
TTBK1 GeneProduct ensembl:ENSG00000146216
REL GeneProduct ncbigene:5966
PLD1 GeneProduct ensembl:ENSG00000075651
PLD2 GeneProduct ensembl:ENSG00000129219
RALBP1 GeneProduct ensembl:ENSG00000017797
RAC1 GeneProduct ensembl:ENSG00000136238
RAC2 GeneProduct ensembl:ENSG00000128340
RAC3 GeneProduct ensembl:ENSG00000169750
CDC42 GeneProduct ensembl:ENSG00000070831
PLCE1 GeneProduct ensembl:ENSG00000138193
PRKCA GeneProduct ensembl:ENSG00000154229
PRKCB GeneProduct ensembl:ENSG00000166501
PRKCG GeneProduct ensembl:ENSG00000126583
RIN1 GeneProduct ensembl:ENSG00000174791
RALBP1 GeneProduct ensembl:ENSG00000017797
ARF6 GeneProduct ensembl:ENSG00000165527
RAC1 GeneProduct ensembl:ENSG00000136238
RAB5A GeneProduct ensembl:ENSG00000144566
RAB5B GeneProduct ensembl:ENSG00000111540
RAB5C GeneProduct ensembl:ENSG00000108774
ABL1 GeneProduct ensembl:ENSG00000097007
ABL2 GeneProduct ensembl:ENSG00000143322
PIK3CA GeneProduct ensembl:ENSG00000121879
PIK3CB GeneProduct ensembl:ENSG00000051382
PIK3CD GeneProduct ensembl:ENSG00000171608
PIK3R1 GeneProduct ensembl:ENSG00000145675
PIK3R2 GeneProduct ensembl:ENSG00000105647
PIK3R3 GeneProduct ensembl:ENSG00000117461

References

  1. KEGG Pathway: hsa04014
  2. The Ras branch of small GTPases: Ras family members don’t fall far from the tree. Reuther GW, Der CJ. Curr Opin Cell Biol. 2000 Apr;12(2):157–65. PubMed Europe PMC Scholia