Fibroblast growth factor receptor (FGFR) mutations, fusions, and rearrangements have been linked to the pathogenesis of multiple tumor types. FGFR2 alterations emerged as oncogenic drivers across a variety types, including Cholangiocarcinoma, lung, Uterine cancer. Approved FGFR inhibitors demonstrated responses in patients that harbor genetic but show reduced activity with gatekeeper molecular ...

Apert syndrome (AS) is a rare type of congenital craniofacial dysmorphic and severe syndactyly the hands feet. Fibroblast growth factor receptor (FGFR) gene mutations are suspect to be involved in this anomaly. The distinct features craniosynostosis-a condition premature closure skull's sutures-, midface hypoplasia-an incomplete development middle face-, syndactyly-webbed fingers or toes-. anor...

Fibroblast growth factors (FGF) are a family of ligands that bind to four different types of cell surface receptor entitled, FGFR1, FGFR2, FGFR3 and FGFR4. These receptors differ in their ligand binding affinity and tissue distribution. The prototypical receptor structure is that of an extracellular region comprising three immunoglobulin (Ig)-like domains, a hydrophobic transmembrane segment an...

Signal transduction by tyrosine kinase growth factor receptors involves ligand-induced phosphorylation of substrates for the kinase, resulting in mediation of common or receptor-specific biological signals. We have compared signal transduction pathways for the fibroblast growth factor receptor-1 (FGFR-1), the platelet-derived growth factor beta-receptor (PDGFR-beta), and a chimeric FGFR-1 molec...

Endochondral ossification is a major mode of bone that occurs as chondrocytes undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. We have identified a role for fibroblast growth factor receptor 3 (FGFR-3) in this process by disrupting the murine Fgfr-3 gene to produce severe and progressive bone dysplasia with enhanced and prolonged endochondral bone growth. This growt...

The Eph receptor tyrosine kinases and their ephrin ligands form a unique cell-cell contact-mediated bidirectional signaling mechanism for regulating cell localization and organization. High expression of Eph receptors in a wide variety of human tumors indicates some roles in tumor progression, which makes these proteins potential targets for anticancer therapy. For this purpose, we did gene exp...

Abstract Extracellular signaling molecules, among them the fibroblast growth factors (FGFs), enable cells to communicate with neighboring cells. Such molecules that receive and transmit a signal require specific tyrosine kinase receptors located at cell surface (fibroblast factor receptors, FGFRs). The binding of molecule its receptor results in dimerization conformational changes cytoplasmic p...

Two competing models for fibroblast growth factor (FGF) receptor (FGFR) dimerization have recently emerged based on ternary FGF-FGFR-heparin crystal structures. In the symmetric two-end model, heparin promotes dimerization of two FGF-FGFR complexes by stabilizing bivalent interactions of the ligand and receptor through primary and secondary sites and by stabilizing direct receptor-receptor cont...

Overexpression of some transmembrane tyrosine kinase growth factor receptors in breast and other tumors has been found to correlate with poor prognosis. Following the cloning of the first two members of the fibroblast growth factor family of receptors (FGFRs), amplification of these receptors in breast carcinomas was found. We have examined 23 breast carcinoma cell lines to determine the extent...