The vertebrate fibroblast growth factor receptor (FGFR) family is an important group of proteins involved in embryonic development and the growth and proliferation of adult cells. Mutations in FGFR proteins can lead to pathologies including bone or limb defects and various forms of cancer. FGFR proteins are receptor tyrosine kinases that, upon ligand binding, dimerize and signal through the MAPK and PLCγ pathways. FGFR1 is a well characterized member of this protein family consisting of an extracellular region, a single-pass transmembrane domain, and the intracellular tyrosine kinase domain. The extracellular region contains a heparin binding domain responsible for interaction with the extracellular matrix while the intracellular domain interacts with downstream effectors after receptor dimerization to propagate signals (1). FGFR1 exists in many alternatively spliced isoforms including a soluble, secreted isoform lacking the transmembrane and kinase domains. While their function is unclear, soluble FGFR1 isoforms may bind to and regulate the activity of FGF ligands during development (1). Typical FGFR1 signaling occurs after ligand binding, receptor dimerization, and phosphorylation of downstream effector proteins. However, recent research has shown internalized FGFR1 is transported to the nucleus where it regulates target gene expression and cell proliferation in cancer cells (2). FGFR1 is a prognostic marker for various cancer types and is amplified or involved in genetic fusions in tumors (3,4).
Monoclonal FGFR1 antibodies have been used in various studies to examine protein-protein interactions or tissue specific expression. In one study by Wang et al. monoclonal FGFR1 antibodies conjugated to sepharose beads were used to purify protein complexes (5). Their study showed FGFR1α and FGFR1β can interact without the kinase domain and in the absence of ligand. Tomlinson and Knowles used monoclonal FGFR1 antibodies in their study of bladder cancer cells (6). They demonstrated elevated expression of FGFR1 splice isoforms in bladder cancer through isoform specific qPCR and through immunohistochemistry using the FGFR1 antibody. The changes in expression levels affected cell sensitivity to FGF1 levels. FGFR1 antibodies can also be used as tools to manipulate cell signaling. Di Maggio et al. used a monoclonal FGFR1 antibody targeting a specific FGFR1 isoform to block and neutralize the receptor (7). This strategy allowed them to identify the signaling requirements for the renewal of bone marrow mesenchymal stem cells.
Novus Biologicals offers FGF R1 reagents for your research needs including:
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