Entry |
|
Name |
Ras signaling pathway - Homo sapiens (human)
|
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 |
Environmental Information Processing; Signal transduction
 |
Pathway map |

 |
Network |
|
Element |
N00001 | EGF-EGFR-RAS-ERK signaling pathway |
N00015 | PDGF-PDGFR-RAS-ERK signaling pathway |
N00019 | FGF-FGFR-RAS-ERK signaling pathway |
N00030 | EGF-EGFR-RAS-PI3K signaling pathway |
N00096 | EGF-EGFR-RAS-RASSF1 signaling pathway |
N00103 | EGF-EGFR-RAS-RalGDS signaling pathway |
N00215 | KITLG-KIT-RAS-ERK signaling pathway |
N00216 | HGF-MET-RAS-ERK signaling pathway |
N00229 | TGFA-EGFR-RAS-ERK signaling pathway |
N00233 | IGF-IGF1R-RAS-ERK signaling pathway |
|
Disease |
H00505 | FGFR3-related short limb skeletal dysplasia |
H00773 | Autosomal dominant mental retardation |
H01437 | Neurofibromatosis type 1 |
H02189 | Neurofibromatosis-Noonan syndrome |
|
Drug |
D00967 | Toremifene citrate (JAN/USAN) |
D02970 | Aprinocarsen sodium (USAN) |
D04014 | Enzastaurin hydrochloride (JAN/USAN) |
D08344 | Tozasertib lactate (USAN) |
D10095 | Cabozantinib s-malate (USAN) |
D10173 | Tivantinib (JAN/USAN/INN) |
D10465 | Golvatinib tartrate (USAN) |
D10800 | Gilteritinib fumarate (JAN/USAN) |
D10891 | Capmatinib hydrochloride (USAN) |
D11073 | Tepotinib hydrochloride hydrate (JAN) |
D11126 | Navicixizumab (USAN/INN) |
D11285 | Ravoxertinib (USAN/INN) |
|
Other DBs |
|
Organism |
Homo sapiens (human) [GN: hsa]
|
Gene |
7039 | TGFA; transforming growth factor alpha [KO:K08774] |
8822 | FGF17; fibroblast growth factor 17 [KO:K04358] |
2255 | FGF10; fibroblast growth factor 10 [KO:K04358] |
8823 | FGF16; fibroblast growth factor 16 [KO:K04358] |
8817 | FGF18; fibroblast growth factor 18 [KO:K04358] |
9965 | FGF19; fibroblast growth factor 19 [KO:K22603] |
8074 | FGF23; fibroblast growth factor 23 [KO:K22428] |
627 | BDNF; brain derived neurotrophic factor [KO:K04355] |
3479 | IGF1; insulin like growth factor 1 [KO:K05459] |
3481 | IGF2; insulin like growth factor 2 [KO:K13769] |
5154 | PDGFA; platelet derived growth factor subunit A [KO:K04359] |
5155 | PDGFB; platelet derived growth factor subunit B [KO:K17386] |
56034 | PDGFC; platelet derived growth factor C [KO:K05450] |
80310 | PDGFD; platelet derived growth factor D [KO:K05450] |
1435 | CSF1; colony stimulating factor 1 [KO:K05453] |
2323 | FLT3LG; fms related tyrosine kinase 3 ligand [KO:K05454] |
7422 | VEGFA; vascular endothelial growth factor A [KO:K05448] |
7423 | VEGFB; vascular endothelial growth factor B [KO:K16858] |
7424 | VEGFC; vascular endothelial growth factor C [KO:K05449] |
2277 | VEGFD; vascular endothelial growth factor D [KO:K05449] |
4804 | NGFR; nerve growth factor receptor [KO:K02583] |
2885 | GRB2; growth factor receptor bound protein 2 [KO:K04364] |
2549 | GAB1; GRB2 associated binding protein 1 [KO:K09593] |
9846 | GAB2; GRB2 associated binding protein 2 [KO:K08091] |
6654 | SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099] |
6655 | SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099] |
10125 | RASGRP1; RAS guanyl releasing protein 1 [KO:K04350] |
10235 | RASGRP2; RAS guanyl releasing protein 2 [KO:K12361] |
25780 | RASGRP3; RAS guanyl releasing protein 3 [KO:K12362] |
7535 | ZAP70; zeta chain of T cell receptor associated protein kinase 70 [KO:K07360] [EC:2.7.10.2] |
27040 | LAT; linker for activation of T cells [KO:K07362] |
3363 | HTR7; 5-hydroxytryptamine receptor 7 [KO:K04163] |
2790 | GNG10; G protein subunit gamma 10 [KO:K04545] |
2791 | GNG11; G protein subunit gamma 11 [KO:K04546] |
2792 | GNGT1; G protein subunit gamma transducin 1 [KO:K04548] |
2793 | GNGT2; G protein subunit gamma transducin 2 [KO:K04549] |
5923 | RASGRF1; Ras protein specific guanine nucleotide releasing factor 1 [KO:K04349] |
5924 | RASGRF2; Ras protein specific guanine nucleotide releasing factor 2 [KO:K12326] |
2902 | GRIN1; glutamate ionotropic receptor NMDA type subunit 1 [KO:K05208] |
2903 | GRIN2A; glutamate ionotropic receptor NMDA type subunit 2A [KO:K05209] |
2904 | GRIN2B; glutamate ionotropic receptor NMDA type subunit 2B [KO:K05210] |
3265 | HRAS; HRas proto-oncogene, GTPase [KO:K02833] |
3845 | KRAS; KRAS proto-oncogene, GTPase [KO:K07827] |
4893 | NRAS; NRAS proto-oncogene, GTPase [KO:K07828] |
5921 | RASA1; RAS p21 protein activator 1 [KO:K04352] |
5922 | RASA2; RAS p21 protein activator 2 [KO:K08053] |
8831 | SYNGAP1; synaptic Ras GTPase activating protein 1 [KO:K17631] |
8437 | RASAL1; RAS protein activator like 1 [KO:K17632] |
9462 | RASAL2; RAS protein activator like 2 [KO:K17633] |
11186 | RASSF1; Ras association domain family member 1 [KO:K09850] |
83593 | RASSF5; Ras association domain family member 5 [KO:K08015] |
7074 | TIAM1; TIAM Rac1 associated GEF 1 [KO:K05731] |
387 | RHOA; ras homolog family member A [KO:K04513] |
5290 | PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153] |
5293 | PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153] |
5291 | PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153] |
5295 | PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649] |
5296 | PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649] |
8503 | PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649] |
8517 | IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210] |
1147 | CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:2.7.11.10] |
4790 | NFKB1; nuclear factor kappa B subunit 1 [KO:K02580] |
5970 | RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735] |
572 | BAD; BCL2 associated agonist of cell death [KO:K02158] |
4301 | AFDN; afadin, adherens junction formation factor [KO:K05702] |
8036 | SHOC2; SHOC2 leucine rich repeat scaffold protein [KO:K19613] |
51365 | PLA1A; phospholipase A1 member A [KO:K13618] [EC:3.1.1.-] |
2002 | ELK1; ETS transcription factor ELK1 [KO:K04375] |
2113 | ETS1; ETS proto-oncogene 1, transcription factor [KO:K02678] |
2114 | ETS2; ETS proto-oncogene 2, transcription factor [KO:K21932] |
9771 | RAPGEF5; Rap guanine nucleotide exchange factor 5 [KO:K08019] |
5906 | RAP1A; RAP1A, member of RAS oncogene family [KO:K04353] |
5908 | RAP1B; RAP1B, member of RAS oncogene family [KO:K07836] |
5900 | RALGDS; ral guanine nucleotide dissociation stimulator [KO:K08732] |
23179 | RGL1; ral guanine nucleotide dissociation stimulator like 1 [KO:K17635] |
5863 | RGL2; ral guanine nucleotide dissociation stimulator like 2 [KO:K17636] |
5966 | REL; REL proto-oncogene, NF-kB subunit [KO:K09254] |
998 | CDC42; cell division cycle 42 [KO:K04393] |
25 | ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2] |
27 | ABL2; ABL proto-oncogene 2, non-receptor tyrosine kinase [KO:K08887] [EC:2.7.10.2] |
5868 | RAB5A; RAB5A, member RAS oncogene family [KO:K07887] |
5869 | RAB5B; RAB5B, member RAS oncogene family [KO:K07888] |
5878 | RAB5C; RAB5C, member RAS oncogene family [KO:K07889] |
382 | ARF6; ADP ribosylation factor 6 [KO:K07941] |
|
Compound |
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 |
|
Reference |
|
Authors |
Malumbres M, Barbacid M |
Title |
RAS oncogenes: the first 30 years. |
Journal |
|
Reference |
|
Authors |
Cox AD, Der CJ |
Title |
Ras history: The saga continues. |
Journal |
|
Reference |
|
Authors |
Cox AD, Der CJ |
Title |
Ras family signaling: therapeutic targeting. |
Journal |
|
Reference |
|
Authors |
Rajalingam K, Schreck R, Rapp UR, Albert S |
Title |
Ras oncogenes and their downstream targets. |
Journal |
|
Reference |
|
Authors |
Schubbert S, Shannon K, Bollag G |
Title |
Hyperactive Ras in developmental disorders and cancer. |
Journal |
|
Reference |
|
Authors |
Poulogiannis G, Luo F, Arends MJ |
Title |
RAS signalling in the colorectum in health and disease. |
Journal |
|
Reference |
|
Authors |
Berndt N, Hamilton AD, Sebti SM |
Title |
Targeting protein prenylation for cancer therapy. |
Journal |
|
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) DOI: 10.2741/3814 |
Reference |
|
Authors |
Rodriguez-Viciana P, Tetsu O, Oda K, Okada J, Rauen K, McCormick F |
Title |
Cancer targets in the Ras pathway. |
Journal |
|
Reference |
|
Authors |
Cox AD, Der CJ |
Title |
The dark side of Ras: regulation of apoptosis. |
Journal |
|
Reference |
|
Authors |
Braun BS, Shannon K |
Title |
Targeting Ras in myeloid leukemias. |
Journal |
|
Reference |
|
Authors |
Pino MS, Chung DC |
Title |
The chromosomal instability pathway in colon cancer. |
Journal |
|
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 |
|
Reference |
|
Authors |
Ahearn IM, Haigis K, Bar-Sagi D, Philips MR |
Title |
Regulating the regulator: post-translational modification of RAS. |
Journal |
|
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 |
|
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 |
|
Reference |
|
Authors |
Kortum RL, Rouquette-Jazdanian AK, Samelson LE |
Title |
Ras and extracellular signal-regulated kinase signaling in thymocytes and T cells. |
Journal |
|
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 |
|
Reference |
|
Authors |
Reuther GW, Der CJ |
Title |
The Ras branch of small GTPases: Ras family members don't fall far from the tree. |
Journal |
|
Reference |
|
Authors |
Fernandez-Medarde A, Santos E |
Title |
The RasGrf family of mammalian guanine nucleotide exchange factors. |
Journal |
|
Reference |
|
Authors |
Iwashita S, Song SY |
Title |
RasGAPs: a crucial regulator of extracellular stimuli for homeostasis of cellular functions. |
Journal |
|
Reference |
|
Authors |
Ory S, Morrison DK |
Title |
Signal transduction: implications for Ras-dependent ERK signaling. |
Journal |
|
Reference |
|
Authors |
Matheny SA, White MA |
Title |
Signaling threshold regulation by the Ras effector IMP. |
Journal |
|
Reference |
|
Authors |
Lemmon MA, Schlessinger J |
Title |
Cell signaling by receptor tyrosine kinases. |
Journal |
|
Reference |
|
Authors |
Skaper SD |
Title |
The neurotrophin family of neurotrophic factors: an overview. |
Journal |
|
Related pathway |
hsa04660 | T cell receptor signaling pathway |
hsa04810 | Regulation of actin cytoskeleton |
|
KO pathway |
|
LinkDB |
 |