Mouse FGFR1c/β-Klotho Assay Kit

Target Background

The family of Fibroblast Growth Factors (FGFs) comprise approximately 23 members that are related by core sequence and structure conservation, with the majority of FGFs being secreted signaling proteins. Secreted FGFs are predominantly autocrine and paracrine factors, with only three members evolved to function as endocrine factors. Paracrine FGFs show high affinity towards the extracellular matrix (ECM) component heparin sulfate (HS) and are thus retained in the ECM and function locally. In contrast, the atypical endocrine subfamily of FGFs, that comprise FGF-19, FGF-21, and FGF-23, have reduced affinity for HS and can therefore escape from the ECM into the circulation to distant reach target distant organs.

This assay utilizes proprietary cells that have been engineered to provide constitutive expression of the Mouse Fibroblast Growth Factor Receptor 1c and Mouse β-Klotho, referred to herein as mFGFR1c/β-Klotho. mFGFR1c and β-Klotho are both single-pass transmembrane proteins. mFGFR1c has an extracellular ligand-binding domain, transmembrane domain, and intracellular tyrosine kinase domain. It has been established that mFGFR1c association with the co-receptor β-Klotho generates a scaffold that is essential for endocrine growth factor binding interactions, such as those with FGF-19 and FGF-212. Following growth factor binding, the activated tyrosine kinase activities of the FGFR initiate intracellular signaling cascades that may include RAS-MAPK, PI3-AKT, PLCγ and/or STAT pathways. For example, activation of the PLCγ pathway leads to an increase of intracellular calcium. One prominent outcome of the FGF/FGFR > PLCγ pathway is that calcineurin, a calcium-dependent phosphatase, dephosphorylates and activates the transcription factor NFAT. It is mFGFR1c/β-Klotho signal transduction via the Ca+2∙calcineurin / NFAT cascade that is exploited by the reporter cells provided in this kit.