Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

K-sam/bek, N-sam/flg and FGFR3/sam3 establish gene family of the receptors for heparin-binding growth factors (HBGFs) or FGFs. These mRNAs were detected in human leukemia cells, CMK, K562 and HEL, which have megakaryocytic phenotype or the potency to differentiate into megakaryocytic lineage. In CMK cells N-sam/flg transcript level was enhanced by the culture with 12-O-tetradecanoylphorbol-13-acetate (TPA). cDNA-polymerase chain reaction identified K-sam/bek mRNA in human platelets, suggesting the involvement of HBGFs in megakaryocytopoiesis and functions of platelets.
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PMID:Expression of the heparin-binding growth factor receptor genes in human megakaryocytic leukemia cells. 131 27

Fibroblast growth factors (FGFs) can influence the growth and differentiation of cultured cells derived from neuroectoderm, ectoderm or mesenchyme. The FGFs interact with a family of at least four closely related receptor tyrosine kinases that are products of individual genes. To investigate the role of FGFs in the growth and differentiation of embryonic tissues and to determine whether the individual FGF receptor genes might have specific functions, we compared the localization of mRNA for two FGF receptor genes, FGFR1 (the flg gene product) and FGFR2 (the bek gene product), during limb formation and organogenesis in mouse embryos (E9.5-E16.5). Although the two genes were coexpressed in some tissues, the differential expression of FGFR1 and FGFR2 in most embryonic tissues was striking. FGFR1 was expressed diffusely in mesenchyme of limb buds, somites and organ rudiments. In contrast, FGFR2 was expressed predominantly in the epithelial cells of embryonic skin and of developing organs. The differential expression of FGFR1 and FGFR2 in mesenchyme and epithelium respectively, suggests the receptor genes are independently regulated and that they mediate different functions of FGFs during development.
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PMID:Two FGF receptor genes are differentially expressed in epithelial and mesenchymal tissues during limb formation and organogenesis in the mouse. 131 77

Fibroblast growth factors (FGFs) and their receptors play an important role in cell growth, angiogenesis and embryonal development. Four distinct genes encoding fibroblast growth factor receptors (FGFRs) were identified: flg, encoding FGFR1, bek encoding FGFR2, and the genes for FGFR3 and FGFR4. Both FGFR2 and keratinocyte growth factor receptor (KGFR) are encoded by the same gene, bek. To study the regulation of expression of the FGF receptors we analysed the DNA sequence flanking the 5' region of the cDNA of murine FGFR2 to seek elements that control its transcription. A 5-kbp fragment containing the 5' end of the cDNA was isolated from mouse genomic library and used to map the promoter region. We found that the sequence encoding the 5' non-translated region of the FGFR2/KGFR cDNA contains an intron located 210 bp upstream from the translation start site. Using RNAase protection and primer extension, we identified the mRNA start 37 bp upstream from the beginning of the bek cDNA. The promoter activity was found to reside in a 1.3-kbp fragment upstream from the cDNA, and deletion mapping further localized the promoter to a 0.7-kbp fragment. The sequence of this region shows high G+C content (62%), which is particularly emphasized in the 200 bp upstream from the mRNA start (80% G+C). This region contains the CCGCCC, GGGCGG AND GGAGG motifs also found in promoters of other growth factor receptors. Neither TATA nor CAAT boxes were found near the RNA start site. The characterization of this promoter will allow studies of the regulation of expression of the FGFR2 during development and in pathophysiological states. The differences between the promoter sequence of the gene for FGFR2 (bek) and FGFR1 (flg) may explain their differential expression during development.
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PMID:Promoter region of the murine fibroblast growth factor receptor 2 (bek/KGFR) gene. 140 37

Fibroblast growth factors (FGFs) and FGF receptors (FGFRs) play major roles in vertebrate embryogenesis, including control of skeletal muscle growth and differentiation. Understanding their roles requires delineating the specific FGF and FGFR isoforms involved. This study analyzes the FGFR transcripts found in a model mouse skeletal myoblast cell line (MM14) during growth and terminal differentiation. MM14 cells express transcripts for FGFR1 (flg) but not FGFR2 (bek). The predominate FGFR1 transcript contains three immunoglobulin (Ig)-like domains in the extracellular ligand binding region. Approximately one-fourth of the three Ig-like domain transcripts possess a 6-nt deletion between the first and second Ig-like domains which after translation would result in deletion of an Arg-Arg pair. Cloning of mouse genomic DNA surrounding the region of the FGFR1 6-nt deletion indicates that the deletion is derived by alternative splicing of FGFR1 transcripts. Transcripts containing two Ig-like domains account for less than 5% of total FGFR1 mRNA in MM14 cells. A survey of RNA from mouse tissues indicated that two Ig-like domain FGFR1 transcripts are rare in all tissues except in lung, in which the two Ig-like domain form accounts for roughly 70% of the lung FGFR1 mRNA. PCR RACE cloning studies disclosed 162 nt of additional FGFR1 5'-flanking RNA which was highly GC-rich. FGFR1 transcripts decline 8- to 10-fold during low serum, (-)FGF-mediated differentiation of MM14 cultures. The kinetics of the FGFR1 mRNA decline is similar to the previously described differentiation-dependent decrease in cell surface FGF receptors.
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PMID:FGF-mediated aspects of skeletal muscle growth and differentiation are controlled by a high affinity receptor, FGFR1. 142 24

Developmental expression of two closely related fibroblast growth factor receptors, bek and flg, is described from early postimplantation until advanced organogenesis. Transcripts of bek and flg were first seen in the primitive ectoderm of egg-cylinder-stage embryos. Later, starting with somitogenesis, and then throughout embryogenesis, they were actively transcribed both in the mesoderm and neuroectoderm. Bek was expressed also in the surface ectoderm and in various epithelia, whereas flg expression was restricted mainly to the mesenchyme. In the limb bud bek transcripts displayed a gradient-like distribution and appeared earlier than flg. The two receptors, in contrast to their almost identical ligand binding specificity, displayed distinct spatial specificities throughout development, suggesting that developmental localization may contribute to functional specificity. The role of bek and flg in gastrulation and in epithelial-mesenchymal interactions of organogenesis will be discussed.
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PMID:Developmental expression of two murine fibroblast growth factor receptors, flg and bek. 166 82

All of 13 human esophageal cancer cell lines contained mRNAs for both basic fibroblast growth factor (bFGF) and its receptor, FGFR1/N-sam protein, while they did not have mRNAs for keratinocyte growth factor (KGF) despite the presence of mRNAs for the KGF receptor gene, K-sam. The results indicate that in human esophageal cancer, bFGF plays roles in an autocrine manner, while KGF acts as a paracrine mediator. In contrast, only one of seven human gastric cancer cell lines contained bFGF mRNAs, while three out of the seven had mRNAs for FGFR1/N-sam protein. The KGF gene was not expressed in any of the gastric cancer cell lines, while K-sam mRNAs were detected in six out of the seven. The results demonstrate that in most human gastric cancers, bFGF does not act as an autocrine mediator, while KGF acts as a paracrine factor. The mRNAs for the other four members of the fibroblast growth factor (FGF) family, including acidic FGF, int-2 protein, hst-1 protein, FGF5 protein and FGF6/hst-2 protein could not be detected in the esophageal and gastric cancer cell lines.
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PMID:Expression of fibroblast growth factor gene family and its receptor gene family in the human upper gastrointestinal tract. 751 92

Signaling via the fibroblast growth factor receptor 1 (FGFR1, flg) was analyzed in Ba/F3 hematopoietic cells expressing either wild-type or a mutant FGF receptor (Y766F) unable to activate phospholipase C-gamma (PLC-gamma) and stimulate phosphatidylinositol (PI) hydrolysis. Stimulation of cells expressing wild-type or mutant FGFR with acidic FGF (aFGF) caused similar activation of Ras. However, an approximately 3-fold reduced activation of Raf-1 and MAP kinase was observed in aFGF-stimulated cells expressing mutant receptors as compared to cells expressing wild-type FGF receptors. Comparison of phosphopeptide maps of Raf-1 immunoprecipitated from the two cell types activated by either aFGF or the phorbol ester (12-O-tetradecanoylphorbol-13-acetate) suggests that Raf-1 is phosphorylated by both Ras-dependent and PLC-gamma-dependent mechanisms. In spite of the differential effect on Raf-1 and MAP kinase activation, aFGF stimulated similar proliferation of cells expressing wild-type or mutant receptors indicating that Ras-dependent activation of Raf-1 and MAP kinase is sufficient for transduction of FGFR mitogenic signals. Ras may also activate signal transduction pathways that are complementary or parallel to the MAP kinase pathway to stimulate cell proliferation.
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PMID:Reduced activation of RAF-1 and MAP kinase by a fibroblast growth factor receptor mutant deficient in stimulation of phosphatidylinositol hydrolysis. 753 87

We studied the correlation between expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and their receptors with vascularity, metastasis, and proliferative index of human colon cancers. Immunohistochemical analyses using antibodies against VEGF, bFGF, their receptors (KDR, flt-1, bek, and flg), factor VIII, and proliferating cell nuclear antigen were carried out on archival specimens of 52 human colon carcinomas and 10 adenomas. Vessels were quantitated by light microscopy (x200), and the intensity of staining for VEGF and bFGF was assessed on a scale of 0-3+. The presence or absence of immunostaining for KDR, flt-1, bek, and flg was evaluated in endothelial cells, and proliferation was determined by counting the number of proliferating cell nuclear antigen-positive cells per 500 tumor cells. Expression of VEGF and KDR was higher in metastatic than in nonmetastatic neoplasms and directly correlated with the extent of neovascularization and the degree of proliferation, whereas expression of bFGF, flt-1, bek, and flg did not differ among tumor types. Vessel counts were greater in metastatic tumors than in nonmetastatic tumors. These findings support the hypothesis that VEGF is an important angiogenic factor in primary and metastatic human colon cancer. VEGF expression and vessel counts may aid in predicting patients at risk for metastasis from colon cancer.
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PMID:Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. 766 63

Fibroblast growth factor receptors (FGFRs) are encoded by at least four distinct highly conserved genes, and alternative splicing generates multiple gene products. The close relationship among different FGFRs has greatly increased the difficulty in generating specific immunochemical probes. As an alternative strategy, we constructed a fusion protein comprising keratinocyte growth factor (KGF) and an IgG1 Fc domain (HFc). The chimeric molecule was efficiently secreted from transfectants as a disulfide-linked dimer that bound KGFRs with high affinity. Moreover, the KGF-HFc, like native KGF, induced DNA synthesis by epithelial cells implying normal functional receptor activation. Because it retained the convenient detection properties of an immunoglobulin, it was possible to use the KGF-HFc in ligand-mediated histochemical analysis of KGFRs. Flow cytometry revealed KGF-HFc chimera detection of the KGFR, an alternative FGFR2 product, but not FGFR1 (flg) or FGFR2 (bek). Histochemical analysis of normal skin demonstrated the specific localization of KGFRs within the spinous layer, a zone of epithelial cell differentiation. KGFRs were also localized to epithelial cells within a specific region of the hair follicle, and they were not detectable in cells of the sweat gland. Tissue sections of soft palate and tonsil, two examples of nonkeratinizing epithelium, revealed staining of stratum spinosum and some staining of the basal cell layer as well. Neither salivary gland epithelium nor lymphoid cells were positive. The ciliated epithelium of the trachea exhibited KGFR expression in intermediate and basal cell layers. In striking contrast to the normal pattern of staining in the adjacent epithelium, a squamous cell carcinoma of skin lacked detectable KGFRs. Our present findings suggest that growth factor-Ig fusion proteins may be generally applicable in ligand-mediated histochemical detection and localization of growth factor receptors.
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PMID:Specific receptor detection by a functional keratinocyte growth factor-immunoglobulin chimera. 772 40

Basic (b) fibroblast growth factor (FGF) mediates various biological responses including mitogenesis and angiogenesis by binding to specific cell surface receptors of the tyrosine kinase family. The bFGF receptor-1 FGFR1) exists in short and long isoforms due to alternate RNA splicing. Minor alterations in the amino acid sequence have also led to reports of different FGFR1 isoforms in different tissues even in the same species. In the absence of any sequence for heart FGFR1 and accumulating evidence for a role of bFGF in heart growth and differentiation, we cloned FGFR1 from embryonic mouse hearts. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to generate full-length short (2259 base pairs) and long (2526 base pairs) forms of FGFR1 cDNAs which generated 86 and 102 kDa proteins, respectively, following in vitro translation. Embryonic mouse heart FGFR1 differed by seven amino acids from the reported sequence for mouse neuroepithelial FGFR1 and appeared more similar to human placental FGFR1. A single FGFR1 transcript of approximately 4.3 kb was seen in RNA isolated from embryonic as well as adult mouse hearts. There was a decrease (approximately 8.5-fold) in FGFR1 RNA levels in the adult. The majority of FGFR1 transcripts in the adult as well as embryonic heart contained exon IIIc (FGFR1-IIIc) which is associated with isoforms that display the highest affinity for bFGF. However, the relative ratio of short versus long FGFR1 RNA expression was 0.5 in the embryonic heart compared to 5.9 in the adult heart. These results indicate that: (i) structurally distinct short and long FGFR1 isoform RNAs are expressed in the embryonic and adult heart; (ii) FGFR1-IIIc is the major form of receptor expressed in the embryonic as well as adult heart; (iii) the transition from the embryo to the adult stage is associated with a decrease but not absence of FGFR1 RNA expression; and (iv) long FGFR1-isoforms are more abundant in the embryo while short FGFR1 isoforms predominate in the adult.
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PMID:Cloning and expression of fibroblast growth factor receptor-1 isoforms in the mouse heart: evidence for isoform switching during heart development. 789 69


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