Disease relevance of FER

• The human tyrosine kinase gene (FER) maps to chromosome 5 and is deleted in myeloid leukemias with a del(5q) [1].
• Both FER and DSR can be used as first-line therapy in hypertension [2].
• During felodipine treatment, 17 patients (12 receiving FER 20 mg) were withdrawn mostly because of vasodilatory side effects such as headache and ankle edema [3].

High impact information on FER

• The cytoplasmic tyrosine kinase FER is associated with the catenin-like substrate pp120 and is activated by growth factors [4].
• In order to understand the cellular function of the FER kinase, we analyzed the effect of growth factor stimulation on the phosphorylation and activity of FER [4].
• The identification of a coiled coil sequence in the FER kinase and the demonstration that the sequence mediates association with a potential substrate suggest a novel mechanism for signal transduction by cytoplasmic tyrosine kinases [4].
• The human and rat FER genes encode a widely expressed 94-kilodalton protein-tyrosine kinase which is antigenically related to the fps/fes protein-tyrosine kinase [5].
• The FER gene is evolutionarily conserved and encodes a widely expressed member of the FPS/FES protein-tyrosine kinase family [5].

Biological context of FER

• The deduced amino acid sequence of FER resembles that of c-fes/fps [6].
• Using a dominant-negative mutant of FER, we provided evidence that FER kinase activity is required for the growth factor-dependent phosphorylation of cortactin [7].
• We have now mapped FER to chromosome 5q14----q23 using in situ hybridization techniques and suggest a more precise location within bands 5q21----q22 [1].
• We report here the complete nucleotide sequence of Sycon raphanus cDNA coding for a 879 aa long protein, which displays high overall similarity in primary structure and organization of domains with non-receptor tyrosine kinases (TKs) from the Fes/FER family [8].
• The human tyrosine kinase gene (FER) detects an RFLP with BgII [9].

Anatomical context of FER

• Our observations provide additional support for a role of FER in mediating signaling from the cell surface, via growth factor receptors, to the cytoskeleton [7].
• Because constituents of the cell-cell contacts are substrates of Fyn and FER, we investigated the effect of shrinkage on the adherens junctions [10].
• These results represent the first biochemical characterization of the cellular FER gene product and also provide a basis for studying the biochemistry of tyrosine kinase function in HeLa cells [11].
• These findings suggested that among the cinnamoyl compounds, CMN was most potent and FER appeared to be a better modulating agent on human malignant cell line [12].

Associations of FER with chemical compounds

• Nuclear and cytoplasmic location of the FER tyrosine kinase [13].
• Exchange of tyrosine residues 421, 466, and 482 for phenylalanine prevented cortactin phosphorylation by hypertonicity and strongly decreased it upon FER overexpression, suggesting that FER targets primarily the same osmo-sensitive tyrosines [10].
• The fractional and molar esterification rates (FER and MER) of cholesterol in plasma and HDL were also determined [14].
• Affinity index (AT value), adsorption heat, X-ray diffraction (XRD), and 13C and 29Si magic-angle spinning (MAS) NMR, FTIR, and Raman spectroscopies were used to study the interaction of highly siliceous MFI-, FAU-, and FER-type zeolites with adsorbed methylamine (MA) [15].
• Felodipine (10 mg) was randomly given as an extended release (FER) tablet in a double-blind, placebo-controlled, cross-over fashion [16].

Regulatory relationships of FER

• Plasma LCAT activity expressed as FER was significantly enhanced by S alone (+33%), and a further increase on drug combination regimen (+58%) was observed [17].

Other interactions of FER

• This FES/FPS-related gene, named FER, lacks the transmembrane and extracellular domains which characterize tyrosine kinases with receptor function [1].
• Using v-abl probes, we have identified and cloned a novel fes/fps-homologous human cDNA, which we have designated FER (pronounced "fair") [6].
• To further understand the function of FER, we have continued our analyses of the interaction of FER with pp120 and other proteins [7].
• Characterization and phylogenetic analysis of a cDNA encoding the Fes/FER related, non-receptor protein-tyrosine kinase in the marine sponge sycon raphanus [8].
• Tyrosine phosphorylation of the TATA element modulatory factor by the FER nuclear tyrosine kinases [18].

Analytical, diagnostic and therapeutic context of FER

• The location of the FER protein within the cell was investigated by using subcellular fractionation and immunofluorescence [13].
• The patients had mild to moderate hypertension and were randomized to receive felodipine ER (FER) 20 mg (n = 50), FER 10 mg (n = 50), or placebo (n = 51) in a 4-week, double-blind, parallel-group multicenter study [3].
• RESULTS: Of 1576 silicotic patients included, 55.6% showed normal spirometry, 28.5% normal forced vital capacity (FVC>or=80% predicted) but reduced forced expiratory ratio (FER<70%), 7.6% reduced FVC but normal FER, and 8.4% reduced both FVC and FER [19].

References