Here we propose the simultaneous inhibition of the FGF‐FGFR pathway and VEGF‐VEGFR pathway. In terms of mechanism, the combination can target tumour cells and tumour microenvironment at the same time (Clin Cancer Res, 2019).

We used X-ray crystallography, NMR spectroscopy, and cell-based assays to demonstrate that recruitment and phosphorylation of Phospholipase Cγ (PLCγ), a prototypical SH2 containing substrate, by FGF receptors (FGFR) entails formation of an allosteric 2:1 FGFR-PLCγ complex.

The diversified role of FGFR partners in regulating FGFR activation and signaling supports the relevance of FGF/FGFR pairs in tumorigenesis. By directly interacting with several co-expressed signaling partners, FGFRs can facilitate, amplify or inhibit key tumor progression processes.

Jul 5, 2000 · Activation of PLC-γ by myristylated FGFR constructs. PLC-γ is tyrosine-phosphorylated and activated in response to FGF stimulation (Mohammadi et al., 1992), and binds to Tyr766 of FGFR1,...

Phospholipase C-gamma (PLC-gamma) is a substrate of the fibroblast growth factor receptor (FGFR; encoded by the flg gene) and other receptors with tyrosine kinase activity.

intracellular receptor substrates FGFR substrate 2 (FRS2) and phospholipase Cg (PLC-g), leading to subsequent upregulation of RAS/mitogen-activated protein kinase (MAPK) and phosphoi-nositide 3-kinase (PI3K)/AKT signaling pathways. Other path-ways can be activated, including STAT-dependent signaling (Fig. 1; refs. 1–5).

We have examined the effects of VEGF and FGF on PLCg phosphorylation and on changes in intracellular Ca21. levels in primary endothelial cells. VEGF stimulation leads to PLCg activation and increases in intracellular Ca21, which are correlated with mitogen-activated protein (MAP) kinase (MAPK) activation and cell growth. Inhibition of Ca21.

Jan 1, 2018 · PLCγ is also required for fibroblast growth factor receptor (FGFR)-driven epithelial to mesenchymal transition (EMT). Reducing PLCγ1 expression using shRNA altered EMT-associated signal molecules at protein and mRNA levels in BGC-823 cells. This suggests that PLCγ is involved in EMT progression in human gastric adenocarcinoma.

Here, we have designed a peptide that contains both the internalization sequence and the FGFR high-affinity binding site for PLC γ, and tested it in cultures of cerebellar neurons for its ability to inhibit the activation of PLC γ by basic FGF.

Nov 3, 2021 · Fibroblast growth factor (FGF) receptors (FGFRs) are highly conserved single transmembrane receptor tyrosine kinases (RTKs), consisting of an extracellular ligand-binding domain and a cytoplasmic conserved tyrosine kinase domain.