Of the 10 FGF transcripts reliably detected, 4 were signific......
Of the 10 FGF transcripts reliably detected, 4 were significantly differentially expressed in the DLPFC of MDD subjects, including 2 FGF receptors (FGFR 2 and 3) and 2 FGF ligands (FGF 1 and 9)More...
Positive relationships between FGF9 and other components at different levels (count: 0)
Positive relationship network of FGF9 in MK4MDD
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Note:
1. The different color of the nodes denotes the level of the nodes.
Genetic/Epigenetic Locus
Protein and Other Molecule
Cell and Molecular Pathway
Neural System
Cognition and Behavior
Symptoms and Signs
Environment
MDD
2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network.
If the mapped gene or protein is not from literature, square node would be used instead of Circle node.
Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node.
Right-click will show also the menus to link to the report page of the node and remove the node and related edges.
Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web
Negative relationships between FGF9 and MDD (count: 0)
Negative relationships between FGF9 and other components at different levels (count: 0)
Five distinct stages have been proposed in the evolution of ......
Five distinct stages have been proposed in the evolution of melanoma on the basis of histological criteria: common acquired and congenital nevi without dysplastic changes; dysplastic nevi with structural and architectural atypia; radial-growth phase (RGP) melanoma; vertical-growth phase (VGP) melanoma; and metastatic melanoma. Oncogenic NRAS mutations activate both effector pathways Raf-MEK-ERK and PI3K-Akt. The Raf-MEK-ERK pathway may also be activated via mutations in the BRAF gene. The PI3K-Akt pathway may be activated through loss or mutation of the inhibitory tumor suppressor gene PTEN. These mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression. Moreover, melanoma development is strongly associated with inactivation of the p16INK4a/CDK4,6/pRb and p14ARF/HMD2/p53 tumor suppressor pathways. The vertical-growth phase and metastatic melanoma are notable for striking changes in the control of cell adhesion. Recently, amplification of the MITF gene was demonstrated in 10% of primary melanomas and 20% of metastatic melanomas, suggesting that MITF is a melanoma oncogene.More...
The mitogen-activated protein kinase (MAPK) cascade is a hig......
The mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals express at least four distinctly regulated groups of MAPKs, extracellular signal-related kinases (ERK)-1/2, Jun amino-terminal kinases (JNK1/2/3), p38 proteins (p38alpha/beta/gamma/delta) and ERK5, that are activated by specific MAPKKs: MEK1/2 for ERK1/2, MKK3/6 for the p38, MKK4/7 (JNKK1/2) for the JNKs, and MEK5 for ERK5. Each MAPKK, however, can be activated by more than one MAPKKK, increasing the complexity and diversity of MAPK signalling. Presumably each MAPKKK confers responsiveness to distinct stimuli. For example, activation of ERK1/2 by growth factors depends on the MAPKKK c-Raf, but other MAPKKKs may activate ERK1/2 in response to pro-inflammatory stimuli.More...
FRS2 is an adapter protein that links FGFR receptors to down......
FRS2 is an adapter protein that links FGFR receptors to downstream MAP kinases. Depending on tissue expression, the products of two FRS2 genes, alpha and beta (the latter also known as FRS3, or SNT-2) serve as an essential core upon which a signaling complex consisting of the tyrosine phosphatase Shp2, the adaptor Grb2, and the docking protein GAB1 is formed, leading to the activation of the RAS-MAP kinase and PI-3-kinase/AKT pathways.More...
The ability of growth factors to protect from apoptosis is p......
The ability of growth factors to protect from apoptosis is primarily due to the activation of the AKT survival pathway. P-I-3-kinase dependent activation of PDK leads to the activation of AKT which in turn affects the activity or expression of pro-apoptotic factors, which contribute to protection from apoptosis. AKT activation also blocks the activity of GSK-3b which could lead to additional antiapoptotic signals.More...
IRS is one of the mediators of insulin signalling events. It......
IRS is one of the mediators of insulin signalling events. It is activated by phosphorylation and triggers a cascade of events involving PI3K, SOS, RAF and the MAP kinases. The proteins mentioned under IRS are examples of IRS family members acting as indicated. More family members are to be confirmed and added in the future.More...
Studies have shown that Shc is phosphorylated in response to......
Studies have shown that Shc is phosphorylated in response to FGF stimulation of cells expressing FGFR. Coprecipitation of Shc had been demonstrated for p66 Shc and FGFR3 and for FGFR1 in mammalian cells expressing the virally encoded form of Src. However it had been suggested that the interaction is indirect, mediated by Src , consistent with earlier observations of FGFR complexes including Src and Shc.More...
FGFs bind and activate alternatively spliced forms of four t......
FGFs bind and activate alternatively spliced forms of four tyrosine kinase FGF receptors in the region between the second and third immunoglobulin domain (known as D2 and D3). The first immunoglobulin domain (D1) and a stretch of acidic residues known as an acid box in the linker between D1 and D2 impart a lower affinity to FGFs compared to receptors in which such regions are removed. FGFRs also contain a short amino acid motif within the second immunoglobulin domain that shares sequence homology with functional motifs present in neural adhesion molecules such as NCAM and N-cadherin. This so called CAM homology domain (CHD) forms a contiguous sequence with the acid box region and is crucial for this mode of activation. Interactions between the neural cell adhesion molecules are important for a number of developmental events and have also been implicated in tumor progression. Although the interaction can be seen over most of the cell surface, it is not seen at points of cell-cell contact where the adhesion molecules accumulate at stable junctions. The FGFR interaction with N-cadherin and NCAM (but not FGF) is absolutely dependant on the presence of the acid box motif. As this motif can be spliced out of all four FGFRs, this suggests a mechanism that can regulate the interaction of the receptor with different ligand classes. From a hormonal point of view, the spatial and temporal expression patterns of FGFs and FGFRs and the ability of specific ligand-receptor pairs to actively signal are important factors regulating FGF activity in a variety of biological processes. FGF signaling activity is regulated by the binding specificity of ligands and receptors and is modulated by extrinsic cofactors such as heparan sulfate proteoglycans.More...
Phospholipase C-gamma (PLC-gamma) is a substrate of the fibr......
Phospholipase C-gamma (PLC-gamma) is a substrate of the fibroblast growth factor receptor (FGFR) and other receptors with tyrosine kinase activity. It is known that the src homology region 2 (SH2 domain) of PLC-gamma and of other signaling molecules (such as GTPase-activating protein and phosphatidylinositol 3-kinase-associated p85) direct their binding toward tyrosine-autophosphorylated regions of the FGFR. PLC activation leads to phosphatidyl inositol (Pt Ins) hydrolysis, release of intracellular calcium and activation of PKC via recruitment of the SH2 domain of PLC-g to the FGFR. Activated PLC-gamma hydrolyzes Pt Ins P2 to form diacylglygerol (DAG) and Ins P3 which stimulates calcium release and activation of calcium/calmodulin dependent protein kinases.More...
Signaling via FGFRs is mediated via direct recruitment of si......
Signaling via FGFRs is mediated via direct recruitment of signaling proteins that bind to tyrosine auto-phosphorylation sites on the activated receptor and via closely linked docking proteins that become tyrosine phosphorylated in response to FGF-stimulation and form a complex with additional complement of signaling proteins. The activation loop in the catalytic domain of FGFR maintains the PTK domain in an inactive or low activity state. The activation-loop of FGFR1, for instance, contains two tyrosine residues that must be autophosphorylated for maintaining the catalytic domain in an active state. In the autoinhibited configuration, a kinase invariant proline residue at the C-terminal end of the activation loop interferes with substrate binding while allowing access to ATP in the nucleotidebinding site. Iin addition to the catalytic PTK core, the cytoplasmic domain of FGFR contains several regulatory sequences. The juxtamembrane domain of FGFRs is considerably longer than that of other receptor tyrosine kinases. This region contains a highly conserved sequence that serves as a binding site for the phosphotyrosine binding (PTB) domain of FRS2. A variety of signaling proteins are phosphorylated in response to FGF stimulation, including Shc, phospholipase-C gamma and FRS2 leading to stimulation of intracellular signaling pathways that control cell proliferation, cell differentiation, cell migration, cell survival and cell shape.More...
FGF9 related interactors from protein-protein interaction data in HPRD (count: 5)