FGF and VEGF signaling network
Schematic of FGF and VEGF signaling network. Signaling is induced by the growth factors binding to their receptors, culminating with phosphorylation of ERK, through the MAPK cascade. MAPK signaling is initiated through the activation of Raf and FRS2 by VEGF and FGF, respectively. The FGF:HSGAG:FGFR1 complex dimerizes and leads to phosphorylation of FRS2 (pFRS2). VEGF binds VEGFR2 to activate Ras, forming Ras-GTP, which further activates Raf (aRaf). Both aRaf and pFRS2 are able to phosphorylate MEK at two sites, and doubly phosphorylated MEK (ppMEK) further phosphorylates ERK. ppERK provides negative feedback on the FGF pathway, as it promotes ubiquitination of FRS2 (FRS2u)
Publication
Mechanistic insight into activation of MAPK signaling by pro-angiogenic factors. (2018) Min Song, et al. BMC Syst Biol. 2018;12:145. Figure: F1.| Organism | Group | Word | Match | Source | NCBI Symbol | NCBI ID |
|---|---|---|---|---|---|---|
| Bos taurus | Mammals | aRaf | ARAF | ncbigene_symbol | ARAF | 540421 |
| Bos taurus | Mammals | FRS2 | FRS2 | ncbigene_symbol | FRS2 | 538624 |
| Bos taurus | Mammals | FGF-2 | FGF-2 | ncbigene_synonym | FGF2 | 281161 |
| Bos taurus | Mammals | FGFR-1 | FGFR1 | ncbigene_symbol | FGFR1 | 281768 |
| Bos taurus | Mammals | VEGF-A | VEGF-A | ncbigene_synonym | VEGFA | 281572 |
| Bos taurus | Mammals | VEGFR-2 | VEGFR2 | ncbigene_synonym | KDR | 407170 |
| Homo sapiens | Primates | Ras-GDP | RAS | famplex_relations | KRAS | 3845 |
| Homo sapiens | Primates | Ras-GDP | RAS | famplex_relations | HRAS | 3265 |
| Homo sapiens | Primates | Ras-GDP | RAS | famplex_relations | NRAS | 4893 |
| Homo sapiens | Primates | Raf | RAF | ncbigene_synonym | ZHX2 | 22882 |
| Homo sapiens | Primates | Raf | RAF | famplex_relations | ARAF | 369 |
| Homo sapiens | Primates | Raf | RAF | famplex_relations | BRAF | 673 |
| Homo sapiens | Primates | Raf | RAF | famplex_relations | RAF1 | 5894 |
| Homo sapiens | Primates | FRS2 | FRS2 | ncbigene_symbol | FRS2 | 10818 |
| Homo sapiens | Primates | ERK | ERK | ncbigene_synonym | EPHB2 | 2048 |
| Homo sapiens | Primates | ERK | ERK | ncbigene_synonym | MAPK1 | 5594 |
| Homo sapiens | Primates | ERK | ERK | famplex_relations | MAPK3 | 5595 |
| Homo sapiens | Primates | PERK | PERK | ncbigene_synonym | EIF2AK3 | 9451 |
| Homo sapiens | Primates | FGF-2 | FGF-2 | ncbigene_synonym | FGF2 | 2247 |
| Homo sapiens | Primates | FGFR-1 | FGFR-1 | ncbigene_synonym | FGFR1 | 2260 |
| Homo sapiens | Primates | VEGF-A | VEGFA | ncbigene_symbol | VEGFA | 7422 |
| Homo sapiens | Primates | VEGFR-2 | VEGFR2 | ncbigene_synonym | KDR | 3791 |
| Homo sapiens | Primates | MEK | MEK | ncbigene_synonym | MAP2K7 | 5609 |
| Homo sapiens | Primates | MEK | MEK | famplex_relations | MAP2K1 | 5604 |
| Homo sapiens | Primates | MEK | MEK | famplex_relations | MAP2K2 | 5605 |
| Rattus norvegicus | Rodents | aRaf | ARAF | ncbigene_symbol | Araf | 64363 |
| Rattus norvegicus | Rodents | FRS2 | FRS2 | ncbigene_symbol | Frs2 | 314850 |
| Rattus norvegicus | Rodents | ERK | ERK | ncbigene_synonym | Ephb1 | 24338 |
| Rattus norvegicus | Rodents | FGF-2 | FGF-2 | ncbigene_synonym | Fgf2 | 54250 |
| Rattus norvegicus | Rodents | FGFR-1 | FGFR-1 | ncbigene_synonym | Fgfr1 | 79114 |
| Rattus norvegicus | Rodents | VEGF-A | VEGF-A | ncbigene_synonym | Vegfa | 83785 |
| Rattus norvegicus | Rodents | VEGFR-2 | VEGFR-2 | ncbigene_synonym | Kdr | 25589 |
| Drosophila melanogaster | Invertebrates | Ras-GDP | RAS | ncbigene_symbol | ras | 43873 |
| Drosophila melanogaster | Invertebrates | Ras-GDP | RAS | ncbigene_synonym | Ras64B | 38494 |
| Drosophila melanogaster | Invertebrates | Ras-GDP | RAS | ncbigene_synonym | Ras85D | 41140 |
| Drosophila melanogaster | Invertebrates | Raf | RAF | ncbigene_symbol | Raf | 31221 |
| Drosophila melanogaster | Invertebrates | ERK | ERK | ncbigene_synonym | Erk7 | 31877 |
| Drosophila melanogaster | Invertebrates | ERK | ERK | ncbigene_synonym | rl | 3354888 |
| Drosophila melanogaster | Invertebrates | PERK | PERK | ncbigene_synonym | PEK | 40653 |
| Drosophila melanogaster | Invertebrates | FGF-2 | FGF-2 | ncbigene_synonym | bnl | 42356 |
| Drosophila melanogaster | Invertebrates | FGFR-1 | FGFR1 | ncbigene_synonym | btl | 39564 |
| Drosophila melanogaster | Invertebrates | VEGF-A | VEGFA | ncbigene_synonym | Pvf1 | 32876 |
| Drosophila melanogaster | Invertebrates | MEK | MEK | ncbigene_synonym | Dsor1 | 31872 |
| Drosophila melanogaster | Invertebrates | MEK | MEK | ncbigene_synonym | Mtk | 36708 |
| Danio rerio | Vertebrates | Ras-GDP | RAS | ncbigene_synonym | rab1ab | 368883 |
| Danio rerio | Vertebrates | aRaf | ARAF | ncbigene_symbol | araf | 403063 |
| Danio rerio | Vertebrates | FRS2 | FRS2 | ncbigene_synonym | frs2b | 436931 |
| Danio rerio | Vertebrates | FGF-2 | FGF2 | ncbigene_symbol | fgf2 | 404231 |
| Danio rerio | Vertebrates | FGFR-1 | FGFR1 | ncbigene_synonym | fgfr1a | 30705 |
| Danio rerio | Vertebrates | VEGF-A | VEGFA | ncbigene_synonym | vegfaa | 30682 |
| Danio rerio | Vertebrates | VEGFR-2 | VEGFR-2 | ncbigene_synonym | kdrl | 796537 |
| Word | Match | MeSH | Name | ChEBI |
|---|---|---|---|---|
| GDP | Guanosine Diphosphate | mesh:D006153 | GDP | chebi:17552 |
Disease mentions
| Word | Match | MeSH | Name | DOID |
|---|---|---|---|---|
| Cancer | NA | |||
| Cardiomyopathy | NA | |||
| Noonan syndrome | NA |