Fibroblast growth factor-1 (FGF-1) is a well characterized growth factor among the 22 members of the FGF superfamily in humans. It binds to all the four known FGF receptors and regulates a plethora of functions including cell growth, proliferation, migration, differentiation, and survival in different cell types. FGF-1 is involved in the regulation of diverse physiological processes such as development, angiogenesis, wound healing, adipogenesis, and neurogenesis. Deregulation of FGF-1 signaling is not only implicated in tumorigenesis but also is associated with tumor invasion and metastasis. Given the biomedical significance of FGFs and the fact that individual FGFs have different roles in diverse physiological processes, the analysis of signaling pathways induced by the binding of specific FGFs to their cognate receptors demands more focused efforts. Currently, there are no resources in the public domain that facilitate the analysis of signaling pathways induced by individual FGFs in the FGF/FGFR signaling system. Towards this, we have developed a resource of signaling reactions triggered by FGF-1/FGFR system in various cell types/tissues. The pathway data and the reaction map are made available for download in different community standard data exchange formats through NetPath and NetSlim signaling pathway resources.
Fibroblast growth factor (FGF) superfamily consists of structurally related polypeptides most of which function through its high affinity fibroblast growth factor receptors (FGFRs). In addition to FGFRs, they also bind to heparan sulfate proteoglycans (HPSGs) and their analog, heparin. These interactions influence the stability of FGFs in the extracellular matrix and also regulate their binding and activation of FGFRs [
Most FGFs have an N-terminal signal peptide and are thus secreted. FGFs 1, 2, 9, 16, and 20 do not have signal peptides. FGFs 9, 16, and 20 may be released through classical secretory pathway; however, FGF-1 and FGF-2 are released from damaged cells or through endoplasmic reticulum-golgi independent exocytotic pathway [
Curated pathway maps are invaluable resources for scientific community. Such comprehensive pathway datasets are being increasingly used in bioinformatics efforts directed towards analysis of high-throughput datasets from various disease contexts. Repositories including Pathway Interaction Database of the National Cancer Institute (
Documentation of specific pathway reactions scattered in the literature into an organized, user-friendly, query-enabled platform is primary to the analysis of signaling pathways. We used NCBI PubMed database to carry out an extensive literature search to retrieve research articles where molecular events triggered by the FGF-1/FGFR signaling system were studied. Specific molecular events screened include (a) physical associations between proteins, (b) posttranslational modifications (PTMs), (c) change in subcellular localization of proteins, (d) activation or inhibition of specific proteins, and (e) regulation of gene expression. Relevant information from research articles were manually documented using the curation tool, PathBuilder. To streamline and organize data collection from literature, we followed the previously described criteria for the inclusion/exclusion of pathway specific reactions [
Canonical FGF/FGFR signaling reactions have been documented in a few public repositories and review articles. Vast amount of literature in the last few years have revealed several novel pathway intermediates of FGF/FGFR signaling system. In order to generate a comprehensive view of FGF/FGFR signaling pathway, we carried out extensive literature search on PubMed for articles pertaining to FGF-1 signaling. Of a total of 3275 articles that were screened, 237 of them had molecular reactions reported downstream of FGF-1 in various cell types/tissues. Manual curation from these research articles revealed 109 molecules involved in FGF-1 induced physical associations, modulation by PTMs, activity, and subcellular or cell surface translocation events. Of the 42 physical associations that were cataloged, 29 were “binary” and 13 were “complex” interactions inclusive of the ligand/receptor interactors. We could record a total of 87 catalysis events, 15 activation/inhibition, and 21 translocation events. The 87 catalysis events include 19 events, where the enzymes directly catalyzing the reactions were studied and reported, and 68 events for which the enzymes which post-translationally modified the proteins are not studied under FGF-1 stimulation. Apart from these molecular reactions, we have also cataloged 117 genes whose expression is reported to be either upregulated or downregulated by FGF-1 treatment. However, only a total of 25 genes were reported to be differentially regulated at mRNA level by FGF-1 stimulation in different human cell types. A list of genes reported to be regulated by FGF-1 in different mammalian systems at the mRNA and/or the protein level is provided in Table
List of genes that are reported to be transcriptionally and translationally regulated by FGF-1 in humans and other mammals.
Gene symbol | Up-/down regulation | mRNA/Protein | Experiment | Organism | Tissue/cell line/type | PubMed ID | Transcriptional regulator | Regulator Gene ID | PubMed ID | |
---|---|---|---|---|---|---|---|---|---|---|
1 | APOE | Up | mRNA and protein | RT-PCR, Western blot | Rat | Astrocytes | 18216067, 19229075, 17548887, 15627653 | |||
2 | BAMBI | Down | mRNA and protein | RT-PCR, Western blot | Human | Preadipocytes | 22187378 | |||
3 | CCND1 | Up | mRNA and protein | Gene chip array, Western blot | Human, rat | MG63 osteoblastic cells, Rat Wister bladder tumor cells (NBT-II) | 15572039, 18189245 | |||
4 | CDK5R1 | Up | mRNA and protein | Q-PCR, Western blot | Rat | PC12 cells | 19249349 | |||
5 | CDKN1A | Up | mRNA and protein | RT-PCR, Western blot | Human, mouse, rat | Chondrocytes, REtsAF cells | 16091747, 16153144, 11779141, 10364154 | STAT1 | 6772 | 11779141, 10364154 |
6 | CEBPA | Up | mRNA and protein | RT-PCR, Western blot | Human, mouse | Preadipocytes, 3T3-L1 cells | 17068114 | |||
7 | CEBPB | Up | mRNA and protein | RT-PCR, Western blot | Human, mouse | Preadipocytes, 3T3-L1 cells | 17068114 | |||
8 | COX2 | Up | mRNA and protein | Northern blot, ELISA | Human, rabbit | Cardiac muscle microvessel endothelial cells | 8790580, 2107185 | |||
9 | EGR1 | Up | mRNA and protein | Q-PCR, Western blot | Mouse, rat | PC12 cells, Hippocampal neuronal cell line HT22, human periodontal ligament cells | 19249349, 20649566, 18179472, 24396070 | STAT3, SP1 | 6774, 6667 | 24396070 |
10 | FOS | Up | mRNA and protein | RT-PCR, northern blot (mouse and rat), Immunohistochemistry, Western blot | Mouse, rat, human | 3T3 cells, Adipocytes, ENU1564 cell, Astrocytes of periventricular zone of third ventricle, SUM-52PE cells | 16309174, 2507555, 18041768, 11172932, 20388777 | |||
11 | JUN | Up | mRNA and protein | RT-PCR, Western blot | Rat | ENU1564 cells | 18041768 | |||
12 | JUNB | Up | mRNA and protein | Gene chip array (Rat), Western blot | Rat, human | Rat Wister bladder tumor cells (NBT-II), SUM-52PE cells | 18189245, 20388777 | |||
13 | MDM2 | Up | mRNA and protein | RT-PCR, Western blot | Rat | REtsAF cells | 16091747 | |||
14 | MMP14 | Up | mRNA and protein | Northern blot, Gene chip array, Western blot | Human, rat | Prostate cancer cell line, LNCaP, Rat Wister bladder tumor cells (NBT-II) | 14673954, 18189245 | STAT3 | 6774 | 14673954 |
15 | MMP9 | Up | mRNA and protein | RT-PCR, Gene chip array, Western blot | Rat | ENU1564 cells, Rat Wister bladder tumor cells (NBT-II) | 18041768, 18189245 | RELA, JUN, FOS | 5970, 3725, 2353 | 18041768 |
16 | MYC | Up | mRNA and protein | Northern blot (Mouse), Western blot | Mouse, human | 3T3 cells, SUM-52PE cells | 16309174, 20388777 | |||
17 | NOS2 | Up | mRNA and protein | RT-PCR, Western blot | Rat | Astrocytes | 16524372 | |||
18 | PLAU | Up | mRNA and protein | RT-PCR, ELISA | Human | Fibroblasts | 12008951 | |||
19 | PPARG | Up | mRNA and protein | RT-PCR, Western blot | Human, mouse | Preadipocytes, 3T3-L1 cells | 17068114, 22187378 | |||
20 | SLC2A4 | Up | mRNA and protein | RT-PCR, Western blot | Human, mouse | Preadipocytes, 3T3-L1 cells | 22187378, 17068114 | |||
21 | THY1 | Up | mRNA and protein | Northern blot, Western blot | Rat | PC12 cell lines | 11084019 | |||
22 | TNFRSF12A | Up | mRNA and protein | RT-PCR, Immunoblot | Rat | Cardiomyocytes | 19629561 | |||
23 | NGF | Up | mRNA and Protein | RT-PCR, Enzyme Immuno assay | Rat | Hippocampal astrocytes, skin fibroblasts, Primary spinal cord astrocyte | 1377078, 15773903 | |||
24 | VEGFA | Up | mRNA and protein | Real time PCR, ELISA | Human | Primary human airway smooth muscle cells | 22205500 | |||
25 | ACPL2 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
26 | ARG1 | Up | mRNA | Gene chip array, Q-PCR | Rat | Rat Wister bladder tumor cells (NBT-II) | 18189245 | |||
27 | ATP2A2 | Up | mRNA | RNA gel blot | Mouse | NIH 3T3 cells | 7506544 | |||
28 | AXIN2 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
29 | BGLAP | Up | mRNA |
|
Mouse | Mouse calvaria cells (coronal sutures) | 12674336 | |||
30 | CTSC | Up | mRNA | Gene chip array | Rat | Rat wister bladder tumor cells (NBT-II) | 18189245 | |||
31 | DKK3 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
32 | DLL1 | Down | mRNA | Northern blot | Mouse | Neuroepithelial precursor (E10) | 11466430 | |||
33 | DUSP1 | Up | mRNA | Gene chip array | Rat | Rat Wister bladder tumor cells (NBT-II) | 18189245 | |||
34 | DYNC2LI1 | Up | mRNA | Gene chip array | Rat | Rat Wister bladder tumor cells (NBT-II) | 18189245 | |||
35 | EDNRA | Up | mRNA | Northern blot | Rat | Arterial smooth muscle cells | 12851419 | |||
36 | EFNB1 | Up | mRNA | Gene chip array | Rat | Rat Wister bladder tumor cells (NBT-II) | 18189245 | |||
37 | ELF4 | Up | mRNA | Gene chip array | Rat | Rat Wister bladder tumor cells (NBT-II) | 18189245 | |||
38 | FASN | Up | mRNA | RNA gel blot | Mouse | NIH 3T3 cells | 7506544 | |||
39 | FGF1 | Up | mRNA | RT-PCR | Rat | Pheochromocytoma cells | 8576258 | |||
40 | FGF7 | Up | mRNA | RT-PCR | Mouse | Embryonic lung mesenchymal cells | 10446271 | |||
41 | FN1 | Up | mRNA | Gene chip array | Rat | Rat Wister bladder tumor cells (NBT-II) | 18189245 | |||
42 | FZD1 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
43 | FZD2 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
44 | FZD7 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
45 | FZD8 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
46 | F3 | Down | mRNA | Northern blot | Human | Human umbilical vein endothelial cells | 9157959 | |||
47 | GADD45A | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
48 | HBEGF | Up | mRNA | Gene chip array | Rat | Rat Wister bladder tumor cells (NBT-II) | 18189245 | |||
49 | HMGA2 | Down | mRNA | Northern blot | Rat | 3T3-L1 cells | 10490844 | |||
50 | IBSP | Up | mRNA |
|
Mouse | Mouse calvaria cells (coronal sutures) | 12674336 | |||
51 | IGF1 | Down | mRNA | RT-PCR | Human | Fibroblasts | 12008951 | |||
52 | IGF2 | Down | mRNA | RT-PCR | Human | Fibroblasts | 12008951 | |||
53 | IGF1R | Down | mRNA | RT-PCR | Human | Fibroblasts | 12008951 | |||
54 | IGF2R | Down | mRNA | RT-PCR | Human | Fibroblasts | 12008951 | |||
55 | IGFBP4 | Down | mRNA | RT-PCR | Human | Fibroblasts | 12008951 | |||
56 | IL4 | Up | mRNA | Q-PCR | Rat | Transected spinal cord tissue | 21411654 | |||
57 | IRS1 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
58 | LAMA3 | Up | mRNA | Gene chip array | Rat | Rat Wister bladder tumor cells (NBT-II) | 18189245 | |||
59 | LRRC17 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
60 | MITF | Up | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
61 | MMP13 | Up | mRNA | Gene chip array, Q-PCR | Rat | Rat Wister bladder tumor cells (NBT-II) | 18189245 | |||
62 | MMP3 | Up | mRNA | Northern blot | Rat | PC12 cell lines | 11084019 | |||
63 | MSH6 | Up | mRNA | RNA gel blot | Mouse | NIH 3T3 cells | 8870641 | |||
64 | MSX2 | Up | mRNA |
|
Mouse | Mouse calvaria cells | 12674336 | |||
65 | NID2 | Up | mRNA | Gene chip array | Rat | Rat Wister bladder tumor cells (NBT-II) | 18189245 | |||
66 | NOTCH1 | Up | mRNA | Northern blot, Gene chip array, Q-PCR | Mouse, rat | Neuroepithelial precursor (E10), bladder tumor cells (NBT-II) | 11466430, 18189245 | |||
67 | NR1H3 | Up | mRNA | RT-PCR | Rat | Astrocytes | 19229075 | |||
68 | ODC1 | Up | mRNA | Northern blot | Mouse | NIH 3T3 cells | 9223379 | |||
69 | PDGFA | Up | mRNA | RNA gel blot | Human | HUVE cells | 1689299 | |||
70 | PFKL | Up | mRNA | RNA gel blot | Mouse | NIH 3T3 cells | 7506544 | |||
71 | PLAT | Up | mRNA | RT-PCR | Human | Fibroblasts | 12008951 | |||
72 | PLAUR | Up | mRNA | RT-PCR | Human | Fibroblasts | 12008951 | |||
73 | PLF | Up | mRNA | Northern blot | Mouse | NIH 3T3 cells | 9223379 | |||
74 | PMEPA1 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
75 | PNRC1 | Up | mRNA | Gene chip array | Rat | Rat Wister bladder tumor cells (NBT-II) | 18189245 | |||
76 | POSTN | Up | mRNA | Northern blot | Rat | Pulmonary arterial smooth muscle cells | 15121739 | |||
77 | PPIA | Up | mRNA | Northern blot | Rat | PC12 cell lines | 11084019 | |||
78 | PRICKLE1 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
79 | PRPH | Up | mRNA | Northern blot | Rat | PC12 cell lines | 11084019 | |||
80 | PTPRE | Up | mRNA | Gene chip array | Rat | Rat Wister bladder tumor cells (NBT-II) | 18189245 | |||
81 | RUNX2 | Up | mRNA |
|
Mouse | Mouse calvaria cells (coronal sutures) | 12674336 | |||
82 | SCGB1A1 | Up | mRNA | RT-PCR | Mouse | Mouse lung epithelium | 12242715 | |||
83 | SDC1 | Up | mRNA | Gene chip array | Rat | Rat Wister bladder tumor cells (NBT-II) | 18189245 | |||
84 | SERPINB1 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
85 | SERPINB2 | Up | mRNA | RT-PCR | Human | Fibroblasts | 12008951 | |||
86 | SERPINE1 | Up | mRNA | RT-PCR | Human | Fibroblasts | 12008951 | |||
87 | SFRP1 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
88 | SFTPC | Up | mRNA | RT-PCR | Mouse | Mouse lung epithelium, Embryonic stem cell (mESC) line E14-Tg2a | 12242715, 20497026 | |||
89 | SOCS1 | Up | mRNA | Northern blot | Rat | Mouse lens epithelium | 14985304 | |||
90 | SOCS3 | Up | mRNA | Northern blot | Rat | Mouse lens epithelium | 14985304 | |||
91 | SOX2 | Up | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
92 | SPP1 | Up | mRNA | Quantitative northern blot | Rat | Pulmonary arterial smooth muscle cells | 15121739 | |||
93 | SPRY1 | Up | mRNA | RNA gel blot | Mouse | MC3T3-E1 osteoblasts | 16604287 | |||
94 | SPRY2 | Up | mRNA | RNA gel blot | Mouse | MC3T3-E1 osteoblasts | 16604287 | |||
95 | SPRY4 | Up | mRNA | RNA gel blot | Mouse | MC3T3-E1 osteoblasts | 16604287 | |||
96 | S1PR3 | Up | mRNA | Northern blot | Human | Human umbilical vein endothelial cells | 9315732 | |||
97 | TCF3 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
98 | TCF4 | Down | mRNA | RT-PCR | Human | Preadipocytes | 22187378 | |||
99 | TGFA | Up | mRNA | Northern blot | Mouse | Cultured keratinocytes | 7535082 | |||
100 | TGFB2 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
101 | TGFBR3 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
102 | THBS1 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
103 | THBS1 | Up | mRNA | Northern blot | Mouse | NIH 3T3 cells | 9223379 | |||
104 | TIMP1 | Up | mRNA | Gene chip array | Rat | Rat Wister bladder tumor cells (NBT-II) | 18189245 | |||
105 | TIMP3 | Down | mRNA | Microarray | Mouse | Osteoblast cells | 18505824 | |||
106 | VIM | Up | mRNA | Gene chip array | Rat | Rat Wister bladder tumor cells (NBT-II) | 18189245 | |||
107 | ADIPOQ | Up | Protein | Radioimmunoassay | Human | Preadipocytes | 17068114 | |||
108 | CCNE1 | Up | Protein | Western blot | Human | MG63 osteoblastic cells | 15572039 | |||
109 | CTNNB1 | Down | Protein | Western blot | Human | Simpson Golabi Behmel syndrome (SGBS), Preadipocytes | 22187378 | |||
110 | HMOX1 | Up | Protein | Western blot | Human | Spinal cord astrocytes | 16524372 | |||
111 | MMP7 | Up | Protein | ELISA | Human | LNCaP cells | 11922392 | STAT3 | 6774 | 11922392 |
112 | PKMYT1 | Up | Protein | Immunoblot | Rat | Chondrosarcoma cells | 21051949 | |||
113 | PLIN1 | Up | Protein | Western blot | Human, mouse | Preadipocytes, 3T3-L1 cells | 17068114 | |||
114 | PTGIS | Down | Protein | ELISA | Human | Endothelial cells | 2107185 | |||
115 | PTGS2 | Down | Protein | ELISA | Human | Endothelial cells | 2107185 | |||
116 | RELA | Up | Protein | Western blot | Rat | ENU1564 cells | 18041768 | |||
117 | RHOA | Up | Protein | Immunoblot | Rat | Cardiomyocytes | 19629561 | |||
118 | SOX9 | Up | Protein | Western blot | Mouse | Costal chondrocytes | 10655493 | |||
119 | WEE1 | Up | Protein | Immunoblot | Rat | Chondrosarcoma cells | 21051949 | |||
120 | CDH2 | Up | Protein | Western blot | Rat | PC12 cells | 24396070 | STAT3, SP1 | 6774, 6667 | 24396070 |
121 | GAP43 | Up | Protein | Western blot | Rat | PC12 cells | 24396070 | STAT3 | 6774 | 24396070 |
Signaling modules comprise a well-characterized group of molecules and their interactions downstream of activation of a receptor. We documented the following signaling modules to be activated upon stimulation with FGF-1.
The Ras/Raf/Mek/Erk pathway has been implicated in cellular processes including cell growth, proliferation, and migration. Stimulation of different cell types with FGF-1 resulted in the formation of multiple complexes involving FRS2, GAB1, SOS1, PTPN11, SHC1, SH2B1, and GRB2 [
The complexes mentioned above also lead to the activation of Pi3k/Akt pathway, another signaling module that regulates various processes including cell growth, survival, cell proliferation, and cell migration [
The c-jun N-terminal kinase
FGF-1 also stimulates STATs (STAT1 and STAT3) and Nf-kB signaling modules. FGFR signaling is reported to be regulated through several downstream molecules including JAK2, SRC, SH2B1, MAPK1/3, MAPK8/9, and STAT3. This signaling axis is known to regulate various cellular processes including neurite outgrowth, cell proliferation, and increased cancer cell invasion [
FGF-1 was found to be involved in a number of biological processes. It is associated with the development of heart [
Functions of FGF-1 identified in diverse cell/tissue types of human and other mammalian origins.
Function | PubMed ID | Cell type/tissue | Organism |
---|---|---|---|
Adipogenesis | 22187378, 17068114 | Preadipocytes | Human |
Apoptosis | 20657013 | Hepatoma cells, HEK293 cells | Human |
15773903 | Motor neuron | Rat | |
9681989 | Peroxynitrite-induced apoptosis in PC12 cells | Rat | |
Cell cycle arrest | 16153144 | cells | Human |
Cell migration | 9108375 | Skin fibroblasts | Human |
11019781 | Fibroblasts | Mouse | |
Cell proliferation | 9182757 | Embryo fibroblasts | Rat |
2441696 | Arterial smooth muscle cells | Human | |
14966081 | AT2 alveolar cells | Human | |
15094393 | Human long-bone growth plate chondrocytes | Human | |
1699952 | Umbilical vein endothelial ceils | Human | |
15767480 | Y79 cells | Human | |
2303528 | Epidermal keratinocytes (BALB-MK1) | Mouse | |
2303528 | Keratinocytes (BALB/MK-1) | Mouse | |
2383402 | Leydig cells (TM3) | Mouse | |
1379845 | Megakaryocyte progenitor cells | Mouse | |
1379845 | Megakaryocytes | Mouse | |
14985304 | Murine lens epithelial cell lines CRLE2, 1AMLE6, TN4-1 and NKR11 | Mouse | |
15574884 | NIH-3T3 cells | Mouse | |
3272188 | Adrenal chromaffin cells | Rat | |
2566605 | Astroblasts | Rat | |
1377078 | Hippocampal astrocytes | Rat | |
2153969 | Rat bladder carcinoma cell line (NBT-II) | Rat | |
8622701 | PC12 cells | Rat | |
8732667 | Prostate cancer cells | Rat | |
1638984 | Retinal cells | Rat | |
1377078 | Skin fibroblasts | Rat | |
12907464 | Aortic smooth muscle cells | Human, rat | |
1638984 | Retinal cells | Rats | |
22108586 | Periodontal fibroblasts | Rat | |
3272188 | Adrenal chromaffin cells | Rat | |
22108586 | Periodontal ligament fibroblasts | Rat | |
20388777 | SUM-52PE cells | Human | |
Cell rounding, growth inhibition | 11779141 | ATDC5 cells, chondroprogenitor cell lines | Mouse |
Cholesterol biosynthesis | 19713443 | Mouse fibroblasts and rat astrocytes | Mouse, rat |
19229075 | Astrocytes | Rat | |
18216067 | Astrocytes | Rat | |
17548887 | Astrocytes | Rat | |
Differentiation | 20497026 | Embryonic stem cell (mESC) line E14-Tg2a | Mouse |
Epithelial-mesenchymal transition | 2153969 | NBT-II cells (Rat bladder carcinoma cell line) | Rat |
7593195 | NBT-II | Rat | |
2153969 | NBT-II | Rat | |
Fiber cell differentiation | 7539358 | Lens epithelial cells | Mouse |
G0/G1 arrest | 21051949 | Chondrosarcoma cells | Rat |
G2 arrest | 21051949 | Chondrosarcoma cells | Rat |
G2/M transition | 20044603 | Breast cancer cells | Human |
Growth arrest | 14593093 | Rat chondrosarcoma (RCS) cells | Rat |
Inhibition of apoptosis | 16524372 | Astrocytes | Rat |
17473910, 16091747 | PC12 and RetsAF cells | Rat | |
Inhibition of cell growth | 17363592 | TAKA-1 cells | Hamster |
Inhibition of neurogenesis | 11466430 | NEP cells | Mouse |
Inhibition of proliferation | 10364154 | Chondrosarcoma cells (RCS) | Rat |
Membrane ruffling | 7534069 | Human ductal breast epithelial tumor cell line (T47D) | Human |
Neurite outgrowth | 20175207 | TREX 293 cells | Human |
3272188 | Adrenal chromaffin cells | Rat | |
8764646 | PC12 cells | Rat | |
19249349 | PC12 cells | Rat | |
3316527, 8576258 | PC12 cells | Rat | |
12127979, 9182757, 2157719 | PC12 cells | Rat | |
Neuronal differentiation | 16716298 | Primary astrocyte from human fetal brain | Human |
7514169, 8622701, 2157719 | PC12 cells | Rat | |
Osteoblast proliferation | 18041768 | ENU1564 cells | Rat |
Osteoblast differentiation | 18505824 | Osteoblasts | Mouse |
Osteogenic differentiation | 12674336 | Sutural mesenchyme in mouse calvaria | Mouse |
Protection from apoptosis | 19765618, 8576258 | PC12 cells | Rat |
Repression of myogenic differentiation | 1379245 | Skeletal muscle myoblasts (MM14) | Mouse |
Retinal cell proliferation | 15978261 | Retinal cells | Mouse |
Skeletal muscle development | 8601591 | Skeletal muscle myoblasts (MM14) | Mouse |
Synaptic plasticity | 20649566 | Hippocampal neuronal cell line HT22 | Mouse |
Tumorigenesis | 20889570 | JMSU1 urothelial carcinoma cell lines | Human |
9038374 | NBD-II | Rat | |
Vascular remodeling | 15121739 | Pulmonary arterial smooth muscle cells (PASMCs) | Rat |
22205500 | ASM (Airway Smooth Muscle cells) | Human | |
Regeneration | 3353388 | Retinal ganglion cells | Rat |
Astrocyte activation | 15773903 | Primary spinal cord astrocyte | Rat |
Neurogenesis | 20429889 | Embryonic stem cells | Mouse |
Wound healing | 9036931 | Mouse | |
Cord Formation | 16631103 | Rat | |
Decrease in food intake | 7692459 | Rat | |
Facilitation of memory | 7692459 | Rat | |
Increase in sleep duration | 8985960 | Rabbit | |
Maintenance of the integrity of the organ of corti, initiation of protective recovery and repair processes following damaging auditory stimuli | 7568115 | Rat | |
Arteriole dilation | 8853345 | Rat | |
Feeding suppressor function | 11172932 | Rat | |
Hair-cell innervation during the terminal development of the sensory epithelium | 12792312 | Rat | |
Lens regeneration | 3792708 | Bovine | |
Lung morphogenesis and differentiation | 12242715 | Rat | |
Metastasis | 1707175 | Rat | |
Muscle regeneration | 1384586 | Mouse | |
Myocardial remodeling | 19629561 | Rat | |
Neuroprotection | 12095987 | Rat | |
Prevention of premature angiogenesis and inflammatory responses | 17643421 | Mouse | |
Protection against hypoxic-ischemic injury | 16635575 | Rat | |
Spinal cord injury repair | 21411654 | Rat | |
Cardioprotection | 15337227, 12176126 | Mouse |
User-friendly visualization of pathways is an important aspect to provide a concise view. A number of tools are available for visualization and analysis of pathway data including Cytoscape [
Network map of FGF-1 signaling. This map manually drawn using PathVisio [
Availability of specific ligand-receptor mediated signaling data in community approved formats is crucial to the understanding of proteins and their reactions in diverse biological processes. Analysis of high-throughput data obtained from microarray- and mass spectrometry-based platforms essentially relies on enrichment of biological function or signaling pathways available in databases to obtain insights into their physiological functions. Although some resources have cataloged FGF signaling in general, this is the first attempt to provide a comprehensive view of FGF-1 signaling. This will be extended to other FGF ligands and/or specific FGFRs in the future to facilitate the analysis of differences between different FGFs and/or FGFRs. The pathway information has been made available through NetPath and NetSlim resources in multiple community standard data formats. The FGF-1 signaling pathway data will be periodically updated in NetPath. We have cataloged multiple signaling modules that are activated upon activation of FGFR and their implications in diverse physiological and pathophysiological processes. We believe that the data presented here will boost further research in this area and will help identify novel therapeutically important molecules that could be targeted in pathological conditions involving aberrant FGF-1 signaling.
S100 calcium binding protein A13
Fibroblast growth factor receptor substrate 2
GRB2-associated binding protein 1
Son of sevenless homolog 1
Protein tyrosine phosphatase, non-receptor type 11
Src homology 2 domain containing transforming protein 1
Growth factor receptor-bound protein 2
Mitogen activated protein kinase
Phosphatidylinositide 3-kinase
v-akt murine thymoma viral oncogene homolog
High density lipoprotein
Jun N-terminal kinase
Signal transducer and activator of transcription 3.
The authors have no conflict of interests.
Shyam Mohan Palapetta, Varot K. Sandhya, and Apeksha Sahu contributed equally to the paper.
The authors thank the Department of Biotechnology (DBT), Government of India, for research support to the Institute of Bioinformatics, Bangalore. Shyam Mohan Palapetta is supported by a Senior Research Fellowship from the Council of Scientific and Industrial Research (CSIR), India. Varot K. Sandhya is a recipient of Inspire Fellowship from the Department of Science and Technology (DST), Government of India. Harsha Gowda is a Wellcome Trust/DBT India Alliance Early Career Fellow.