Skip to main content
An official website of the United States government

What Do We Mean By "RAS Pathway"?

, by Frank McCormick

Frank McCormick, Ph.D.

Dr. Frank McCormick directs the research efforts of the RAS Initiative at FNLCR.

Dear all,

We are planning a paper that presents a RAS-centric view of the data in TCGA.  This will be a collaboration between Gaddy Getz and colleagues at the Broad, and Bob Stephens and colleagues at the Frederick National Lab and others. The aim is to provide a synopsis of expression patterns, mutations and copy number changes, and several other parameters relevant to the RAS pathway across the  different tumor types.

As you all know, this pathway can be defined in various ways. For purposes of interrogating TCGA data we have used gene names from the Broad Tumor Portal. Some may not be familiar to you. For example, I hadn’t realized that ARHGAP35, which is mutated at quite a high frequency, is actually  p190RhoGAP, made popular by Jeff Settleman. Matt Meyerson kindly pointed this out to me.

 

Diagram outlining the RAS signaling pathway. It includes human gene symbols and shows the flow of signals through various proteins and complexes. Proteins within complexes are separated by colons. Black arrows indicate activation, while red lines represent inhibition. The diagram illustrates interactions between growth factors and components such as RAS, RAF, MEK, and ERK, as well as other related pathways like PI3K/AKT and mTOR.

The diagram shows 118 genes arranged in 36 groups containing one to eleven genes per group.  The proteins represented by gene names in a group are thought to carry out similar, but probably not identical, functions. Gene names separated by periods represent proteins believed to form physical complexes. At the top of the diagram "growth factors" signal through receptors and messengers to the three RAS proteins. The RAS proteins in turn signal through three alternative pathways to affect many downstream targets including TP53, RB1, and MTOR.  Arrows represent activation signals, dotted  "T" lines represent inhibitory signals. The bracket connecting KSR1 and KSR2 to the RAF, MAP2K, and MAPK genes represents a scaffolding function.

Anyway, we'd be very grateful  if you could send suggestions for genes that we missed or errors in the pathway diagram.  Any other suggestions for making this effort more useful would be welcome, particularly in the context of how to best share the TCGA data in the most useful way possible.

Provide your feedback by commenting below or email me at SolveRAS@nih.gov.

Cheers,

Frank

 

Gene Names, Cognate Proteins, and Aliases in the RAS Pathway

The table comprises the name of each human gene in the RAS Pathway diagram,  the name of the cognate protein for each gene, and gene aliases (alternative names).  The aliases in bold are gene names more commonly used by RAS researchers.

Gene nameProtein name from Uniprot or BioGPSAlternative gene names from BioGPS
AKT1RAC-alpha serine/threonine-protein kinaseAKT, CWS6, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA
AKT2RAC-beta serine/threonine-protein kinase HIHGHH, PKBB, PKBBETA, PRKBB, RAC-BETA
AKT3RAC-gamma serine/threonine-protein kinaseMPPH, MPPH2, PKB-GAMMA, PKBG, PRKBG, RAC-PK-gamma, RAC-gamma, STK-2
ALKAnaplastic lymphoma receptor tyrosine kinase; ALK tyrosine kinase receptorCD246, NBLST3
ARAFSerine/threonine-protein kinase A-Raf A-RAF, ARAF1, PKS2, RAFA1
ARHGAP35Rho GTPase-activating protein 35 GRF-1, GRLF1, P190-A, P190A, p190ARhoGAP, p190RhoGAP
BRAFSerine/threonine-protein kinase B-raf B-RAF1, BRAF1, NS7, RAFB1
CCND1Cyclin D1BCL1, D11S287E, PRAD1, U21B31
CDK4Cyclin-dependent kinase 4CMM3, PSK-J3
CDK6Cyclin-dependent kinase 6PLSTIRE
DUSP1Dual specificity phosphatase 1CL100, HVH1, MKP-1, MKP1, PTPN10
DUSP2Dual specificity phosphatase 2PAC-1, PAC1
DUSP3Dual specificity phosphatase 3VHR
DUSP4Dual specificity phosphatase 4HVH2, MKP-2, MKP2, TYP
DUSP5Dual specificity phosphatase 5DUSP, HVH3
DUSP6Dual specificity phosphatase 6HH19, MKP3, PYST1
EGFREpidermal growth factor receptorERBB, ERBB1, HER1, PIG61, mENA
EIF4EBP1Eukaryotic translation initiation factor 4E-binding protein 1 4E-BP1, 4EBP1, BP-1, PHAS-I
ERBB2Receptor tyrosine-protein kinase erbB-2CD340, HER-2, HER-2/neu, HER2, MLN 19, NEU, NGL, TKR1
ETS1v-ets avian erythroblastosis virus E26 oncogene homolog 1ETS-1, EWSR2, p54
ETS2v-ets avian erythroblastosis virus E26 oncogene homolog 2ETS2IT1
FGFR1Fibroblast growth factor receptor 1BFGFR, CD331, CEK, FGFBR, FGFR-1, FLG, FLT-2, FLT2, HBGFR, HH2, HRTFDS, KAL2, N-SAM, OGD, bFGF-R-1
FGFR2Fibroblast growth factor receptor 2BBDS, BEK, BFR-1, CD332, CEK3, CFD1, ECT1, JWS, K-SAM, KGFR, TK14, TK25
FGFR3Fibroblast growth factor receptor 3CH, CD333, CEK2, HSFGFR3EX, JTK4
FGFR4Fibroblast growth factor receptor 4CD334, JTK2, TKF
FOSFBJ murine osteosarcoma viral oncogene homologAP-1, C-FOS, p55
GRB2Growth factor receptor-bound protein 2 ASH, EGFRBP-GRB2, Grb3-3, MST084, MSTP084, NCKAP2
HRASGTPase HRasC-BAS/HAS, C-H-RAS, C-HA-RAS1, CTLO, H-RASIDX, HAMSV, HRAS1, RASH1, p21ras
JUNJun proto-oncogeneAP-1, AP1, c-Jun
KRASGTPase KRasC-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A, K-RAS4B, KI-RAS, KRAS1, KRAS2, NS, NS3, RASK2
KSR1Kinase suppressor of Ras 1 KSR, RSU2
KSR2Kinase suppressor of Ras 2[none]
MAP2K1Dual specificity mitogen-activated protein kinase kinase 1CFC3, MAPKK1, MEK1, MKK1, PRKMK1
MAP2K2Dual specificity mitogen-activated protein kinase kinase 2CFC4, MAPKK2, MEK2, MKK2, PRKMK2
MAPK1Mitogen-activated protein kinase 1 ERK, ERK-2, ERK2, ERT1, MAPK2, P42MAPK, PRKM1, PRKM2, p38, p40, p41, p41mapk, p42-MAPK
MAPK3Mitogen-activated protein kinase 3ERK-1, ERK1, ERT2, HS44KDAP, HUMKER1A, P44ERK1, P44MAPK, PRKM3, p44-ERK1, p44-MAPK
MDM2MDM2 proto-oncogene, E3 ubiquitin protein ligaseACTFS, HDMX, hdm2
METMET proto-oncogene, receptor tyrosine kinase; hepatocyte growth factor receptorAUTS9, HGFR, RCCP2, c-Met
MLST8MTOR associated protein, LST8 homolog (S. cerevisiae)GBL, GbetaL, LST8, POP3, WAT1
MTORMechanistic target of rapamycin (serine/threonine kinase)FRAP, FRAP1, FRAP2, RAFT1, RAPT1
NF1NeurofibrominNFNS, VRNF, WSS
NRASGTPase NRasALPS4, CMNS, N-ras, NCMS, NRAS1, NS6
PAK1p21 protein (Cdc42/Rac)-activated kinase 1PAKalpha
PAK2p21 protein (Cdc42/Rac)-activated kinase 2PAK65, PAKgamma
PAK3p21 protein (Cdc42/Rac)-activated kinase 3 CDKN1A, MRX30, MRX47, OPHN3, PAK3beta, bPAK, hPAK3
PAK4p21 protein (Cdc42/Rac)-activated kinase 4[none]
PDGFRAPlatelet-derived growth factor receptor alphaCD140A, PDGFR-2, PDGFR2, RHEPDGFRA
PDGFRBPlatelet-derived growth factor receptor betaCD140B, IBGC4, IMF1, JTK12, PDGFR, PDGFR-1, PDGFR1
PDPK13-phosphoinositide-dependent protein kinase 1 PDK1, PDPK2, PRO0461
PIK3CAPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform CLOVE, CWS5, MCAP, MCM, MCMTC, PI3K, p110-alpha
PIK3CBPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform P110BETA, PI3K, PI3KBETA, PIK3C1
PIK3CDphosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit deltaAPDS, IMD14, P110DELTA, PI3K, p110D
PIK3R1Phosphatidylinositol 3-kinase regulatory subunit alphaAGM7, GRB1, p85, p85-ALPHA
PIK3R2Phosphatidylinositol 3-kinase regulatory subunit betaMPPH, MPPH1, P85B, p85, p85-BETA
PIK3R3Phosphatidylinositol 3-kinase regulatory subunit gammap55, p55-GAMMA
PIK3R4Phosphoinositide 3-kinase regulatory subunit 4 VPS15, p150
PIK3R5Phosphoinositide 3-kinase regulatory subunit 5F730038I15Rik, FOAP-2, P101-PI3K, p101
PIK3R6Phosphoinositide 3-kinase regulatory subunit 6  C17orf38, HsT41028, p84 PIKAP, p87(PIKAP), p87PIKAP
PRKAA15'-AMP-activated protein kinase catalytic subunit alpha-1AMPK, AMPKa1
PRKAA25'-AMP-activated protein kinase catalytic subunit alpha-2  AMPK, AMPK2, AMPKa2, PRKAA
PRKAB15'-AMP-activated protein kinase subunit beta-1  AMPK, HAMPKb
PRKAB25'-AMP-activated protein kinase subunit beta-2[none]
PRKAG1Protein kinase, AMP-activated, gamma 1 non-catalytic subunitAMPKG
PRKAG2Protein kinase, AMP-activated, gamma 2 non-catalytic subunitAAKG, AAKG2, CMH6, H91620p, WPWS
PRKAG3Protein kinase, AMP-activated, gamma 3 non-catalytic subunitAMPKG3
PTENPhosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN10q23del, BZS, CWS1, DEC, GLM2, MHAM, MMAC1, PTEN1, TEP1
RAC1Ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)Rac-1, TC-25, p21-Rac1
RAC2Ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2)EN-7, Gx, HSPC022, p21-Rac2
RAC3Ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3)[none]
RAF1RAF proto-oncogene serine/threonine-protein kinaseCMD1NN, CRAF, NS5, Raf-1, c-Raf
RALARas-related protein Ral-ARAL
RALBRas-related protein Ral-B[none]
RALGDSRal guanine nucleotide dissociation stimulator  RGDS, RGF, RalGEF
RASA1Ras GTPase-activating protein 1 CM-AVM, CMAVM, GAP, PKWS, RASA, RASGAP, p120GAP, p120RASGAP
RASA2Ras GTPase-activating protein 2GAP1M
RASA3Ras GTPase-activating protein 3GAP1IP4BP, GAPIII
RASAL1RasGAP-activating-like protein 1 RASAL
RASAL2Ras GTPase-activating protein nGAP NGAP
RASAL3RAS protein activator like-3 [none]
RASGRF2Ras-specific guanine nucleotide-releasing factor 2GRF2, RAS-GRF2
RASGRP1RAS guanyl-releasing protein 1CALDAG-GEFI, CALDAG-GEFII, RASGRP, V, hRasGRP1
RASGRP2RAS guanyl-releasing protein 2CALDAG-GEFI, CDC25L
RASGRP3Ras guanyl-releasing protein 3 GRP3, KIAA0846
RASGRP4RAS guanyl-releasing protein 4[none]
RB1Retinoblastoma 1OSRC, PPP1R130, RB, p105-Rb, pRb, pp110
RHEBRas Homolog Enriched In Brain, GTP-binding protein RhebRHEB2
RHOARas homolog family member AARH12, ARHA, RHO12, RHOH12
RHOBRas homolog family member BARH6, ARHB, MST081, MSTP081, RHOH6
RHOCRas homolog family member CARH9, ARHC, H9, RHOH9
ROCK1Rho-associated, coiled-coil containing protein kinase 1P160ROCK, ROCK-I
ROCK2Rho-associated, coiled-coil containing protein kinase 2ROCK-II
ROS1ROS proto-oncogene 1 , receptor tyrosine kinaseMCF3, ROS, c-ros-1
RPS6KA1Ribosomal protein S6 kinase alpha-1  MAPKAPK1A, RSK1
RPS6KA2Ribosomal protein S6 kinase alpha-2  HU-2, MAPKAPK1C, RSK, RSK3, S6K-alpha, S6K-alpha2, p90-RSK3, pp90RSK3
RPS6KA3Ribosomal protein S6 kinase alpha-3  CLS, HU-3, ISPK-1, MAPKAPK1B, MRX19, RSK, RSK2, S6K-alpha3, p90-RSK2, pp90RSK2
RPS6KA4Ribosomal protein S6 kinase alpha-4  MSK2, RSK-B
RPS6KA5Ribosomal protein S6 kinase alpha-5MSK1, MSPK1, RLPK
RPS6KA6Ribosomal protein S6 kinase alpha-6PP90RSK4, RSK4
RPTORRegulatory associated protein of MTOR, complex 1KOG1, Mip1
SHC1SHC (Src homology 2 domain containing) transforming protein 1SHC, SHCA
SHC2SHC (Src homology 2 domain containing) transforming protein 2SCK, SHCB, SLI
SHC3SHC (Src homology 2 domain containing) transforming protein 3N-Shc, NSHC, RAI, SHCC
SHC4SHC (Src homology 2 domain containing) transforming protein 4RaLP, SHCD
SOS1Son of sevenless homolog 1GF1, GGF1, GINGF, HGF, NS4
SOS2Son of sevenless homolog 2[none]
SPRED1Sprouty-related, EVH1 domain-containing protein 1NFLS, PPP1R147, hSpred1, spred-1
SPRED2Sprouty-related, EVH1 domain-containing protein 2 Spred-2
SPRED3Sprouty-related, EVH1 domain-containing protein 3 Eve-3, spred-3
SPRY1Protein sprouty homolog 1 hSPRY1
SPRY2Protein sprouty homolog 2 hSPRY2
SPRY3Protein sprouty homolog 3HSPRY3, spry-3
SPRY4Protein sprouty homolog 4  HH17
STK11Serine/threonine-protein kinase STK11LKB1, PJS, hLKB1
TIAM1T-lymphoma invasion and metastasis-inducing protein 1[none]
TIAM2T-lymphoma invasion and metastasis-inducing protein 2STEF, TIAM-2
TP53tumor protein p53BCC7, LFS1, P53, TRP53
TSC1Tuberous Sclerosis 1, HamartinLAM, TSC
TSC2Tuberous Sclerosis 2,  TuberinLAM, PPP1R160, TSC4

< Older Post

The RAS Initiative - Welcome

Newer Post >

Quantitative Assays for RAS Pathway Proteins and Phosphorylation States

If you would like to reproduce some or all of this content, see Reuse of NCI Information for guidance about copyright and permissions. In the case of permitted digital reproduction, please credit the National Cancer Institute as the source and link to the original NCI product using the original product's title; e.g., “What Do We Mean By "RAS Pathway"? was originally published by the National Cancer Institute.”

Archive

Email