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

---

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

We have previously cloned and sequenced a newt keratinocyte growth factor receptor (KGFR) cDNA which exhibited a unique spatial and temporal expression pattern in the regenerating newt limb. In this report, we further characterize the biochemical and functional properties of this newt KGFR. A stable Chinese hamster ovary transfectant overexpressing the newt KGFR was capable of binding both 125I-fibroblast growth factor-1 (FGF-1) and 125I-FGF-7 but not 125I-FGF-2, indistinguishable from the human KGFR. Scatchard analysis and cross-linking studies further support the conclusion that FGF-1 and FGF-7 are the ligands for the newt KGFR. In addition to their ability to bind to FGFs, both the human and the newt KGFR are also capable of repressing differentiation in mouse MM14 myoblasts. MM14 cells express FGFR1 and are repressed from differentiation by FGF-1, FGF-2, and FGF-4 but not FGF-7. Co-transfection of MM14 cells with either a human or newt KGFR expression construct conferred a response to FGF-7 as determined by a human alpha-cardiac actin/luciferase reporter construct. The response to FGF-7 was similar to the endogenous FGF response as FGF-7 prevented MM14 myoblasts from undergoing terminal differentiation. Thus, both the human and the newt KGFRs transduce signals similar to those transduced via the endogenous mouse FGFR1. Together these data indicate that this newly isolated newt KGFR is a functional receptor as it binds two FGF family members with high affinity and mediates signaling in skeletal muscle myoblasts. Because the binding pattern of the newt KGFR is similar to the pattern observed for its mammalian counterpart, it emphasizes the strict conservation that this ligand/receptor system has undergone through evolution.
...
PMID:Conservation of ligand specificity between the mammalian and amphibian fibroblast growth factor receptors. 749 35

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.
...
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 have previously shown, by in situ hybridization, that fibroblast growth factor receptor 2 (FGFR2) is present in the basal layer of wound epithelium during limb regeneration in newts (Notophthalmus viridescens). In contrast, FGFR1 expression is observed throughout the blastema mesenchyme but is distinctly absent from the wound epithelium (Poulin et al. [1993] Development 119:353-361). Sequence analysis revealed that we have isolated both the KGFR and bek variants of FGFR2. These two variants differ only in the second half of the last of their three (or two) Ig-like domains. In this report, we show the expression patterns of FGFR2 variants during limb regeneration by in situ hybridization. During the pre-blastema stages of regeneration, FGFR2 expression was observed in the basal layer of the wound epithelium and in the cells of the periosteum. The wound epithelial hybridization was observed when the KGFR-specific probe was used while the bek-specific probe hybridized to mRNA in the cells of the periosteum. As regeneration progresses to the blastema stages, KGFR expression continued to be observed in the basal layer of the wound epithelium with additional hybridization seen in the blastema mesenchyme closely associated with the bisected bones. The bek-specific hybridization pattern observed at this stage corresponds specifically to the mesenchymal hybridization. In the differentiation stages of regeneration, the mesenchymal expression of FGFR2 becomes restricted to the cells of the condensing cartilage and later to the perichondrium. Interestingly, there appears to be a dorsoventral gradient of the expression of both KGFR and bek variants of FGFR2, which are opposite each other at the later stages of regeneration. Thus, re-programming of expression of the two FGFR2 variants is required during the initial wound closure of limb regeneration. Remarkably, the expression patterns of KGFR and bek mimic those observed in the mouse limb bud during early embryonic development (Orr-Urtreger et al. [1993] Dev. Biol. 18:475-486). Moreover, our results suggest that the two FGFR2 variants have distinct roles in limb regeneration. Further investigation regarding the potential sources of the FGF ligands will help establish the roles that FGFs and FGFRs play in limb regeneration.
...
PMID:Re-programming of expression of the KGFR and bek variants of fibroblast growth factor receptor 2 during limb regeneration in newts (Notophthalmus viridescens). 762 94

The murine fibroblast growth factor receptor 2 (FGFR2) and keratinocyte growth factor receptor (KGFR) are two products of the same gene which display distinct binding specificities. We and others have shown that a major structural element underlying this functional divergence is a variable 50 amino acids long region constituting the C-terminal half of the third immunoglobulin (Ig)-like domain of the receptor. This region of the two receptors is encoded by two distinct exons which are alternatively used in cells of different tissues and origin. To further investigate the role of this confined variable region in determining ligand binding specificity we have generated a chimeric molecule between FGFR1 and KGFR where the variable segment of KGFR replaces the homologous region in FGFR1. Binding studies as well as chemical crosslinking of radiolabeled ligands revealed that the recombinant FGFR1/KGFR chimera has retained the binding affinity to acidic FGF and FGF4 (hst/kfgf) but lost the capacity to bind basic FGF (bFGF). This chimeric receptor bound keratinocyte growth factor (KGF), however, with significantly lower affinity as compared with KGFR. High affinity binding of KGF was acquired only when also domain 2 in this chimera was replaced by its homologous domain from FGFR2. These results demonstrate that ligand binding and specificity involves multiple receptor elements which are located at both Ig-like domain 2 and 3 of FGF receptors.
...
PMID:Multiple structural elements determine ligand binding of fibroblast growth factor receptors. Evidence that both Ig domain 2 and 3 define receptor specificity. 768 32

The immunohistochemical localizations of acidic and basic fibroblast growth factor (aFGF and bFGF) were investigated in the striatum and midbrain of Huntington's disease (HD) and control cases using specific antibodies. In the striatum of control cases, the ependymal cell layer was stained for aFGF and bFGF. In addition, a few subependymal astrocytes were positive for aFGF, and some neurons stained weakly for bFGF. In HD striatum, many astrocytes and remaining neurons were strongly stained for aFGF. aFGF-positive astrocytes were particularly conspicuous in the subependymal region of the caudate but appeared throughout the caudate and putamen. The number of bFGF-positive astrocytes was slightly increased. In contrast to the caudate/putamen, the globus pallidus, nucleus of the oculomotor nerve and substantia nigra showed very similar patterns for both aFGF and bFGF in control and most HD brains. Reports that FGF can protect against glutamate neurotoxicity, and that the FGF receptor (FGFR3), with its gene located in the HD region on chromosome 4, appears in striatal neurons, make it tempting to speculate on a possibly important role for FGF-FGFR3 interactions in HD pathology.
...
PMID:Acidic and basic fibroblast growth factor-like immunoreactivity in the striatum and midbrain in Huntington's disease. 768 78

Several chromosomal regions are found to be consistently amplified in human breast cancers. For two of these regions, 8p12 and 10q26, we previously reported the amplification of genes encoding FGF receptors, FGFRI/FLG and FGFR2/BEK, in about 12% of breast tumors. The PLAT gene, encoding the tissue-type plasminogen activator, is also located close to or within the 8p12 region. In the present study, we show that both FGFRI and PLAT can be amplified in breast as well as ovarian carcinomas. FGFRI amplification was detected in 14.5% of breast and 7.8% of ovarian tumors, whereas PLAT was found to be amplified in 15.6% and 19.4% of the tumors, respectively. Each gene could be amplified independently of the other. These data raised the question of which gene is selected for amplification at 8p12. In most cases, the levels of expression of FGFRI and PLAT in breast tumors were comparable to their level of expression in normal mammary tissue. However, FGFRI was expressed above the normal level in a certain number of cases. This gene could be a good candidate as "driver" of the 8p12 amplification, but it cannot account for all complex molecular events taking place in this region.
...
PMID:FGFRI and PLAT genes and DNA amplification at 8p12 in breast and ovarian cancers. 769 48

The family of FGF growth factors is involved in several biological processes and might play an important role in tumorigenesis. We have studied the respective expression of 8 of the 9 characterized FGF genes, and of the 4 known FGF receptor genes, in a panel of 10 tumor-cell lines and 103 breast-tumor samples, using RT-PCR and Northern-blot analyses. FGF1 and FGF2 were expressed in almost all samples, while expression of FGF5, FGF6, FGF7, and FGF9 was more restricted. FGFR1, FGFR2 and FGFR4 were expressed at high levels in respectively 22%, 4% and 32% of tumors. FGFR3 expression was not detected. The transcript encoding an FGFR1 isoform with 2 immunoglobulin-like domains was the most prevalent.
...
PMID:Expression of FGF and FGF receptor genes in human breast cancer. 770 43

We described previously that acidic fibroblast growth factor (aFGF), but not basic fibroblast growth factor (bFGF), can induce the rat carcinoma cell line NBT-II to undergo a rapid and reversible transition from epithelial to mesenchymal phenotype (EMT). We now find that NBT-II EMT is stimulated by keratinocyte growth factor (KGF) in cells grown at low density. Accordingly, a high-affinity receptor showing 98% homology to mouse FGF receptor 2b/KGF receptor was cloned and sequenced from NBT-II cells. Northern analysis indicated that mRNA for FGF receptor 2b/KGF receptor was drastically down-regulated within 1 wk in aFGF-induced mesenchymal NBT-II cells. This decrease coincided with an up-regulation of FGF receptor 2c/Bek, a KGF-insensitive, alternatively spliced form of FGF receptor 2b/KGF receptor. Functional studies confirmed that KGF could not maintain EMT induction on mesenchymal NBT-II cells. FGF receptor 1 and FGF receptor 2c/Bek could also support EMT induction when transfected into NBT-II cells in response to aFGF or bFGF. Such transfected cells could bind bFGF as well as aFGF. Therefore, EMT can be induced through different FGF receptors, but EMT may also regulate FGF receptor expression itself.
...
PMID:Alternative splicing in fibroblast growth factor receptor 2 is associated with induced epithelial-mesenchymal transition in rat bladder carcinoma cells. 780 53

Protein tyrosine kinases have been implicated in tumor initiation and progression. Here we used Northern blotting to study expression of their genes in cultured normal melanocytes and 19 melanoma cell lines from different stages of tumor progression. We detected transcripts for 2 cytoplasmic (ABL and FES) and 6 receptor (ECK, ERB-B2, FGF-R4, IGFI-R, KDR and TIE) kinases but not for receptors RET or TRK-A. Genes for ECK, FGF-R4 and TIE were expressed ectopically in melanomas (not in normal melanocytes). Similarly, ECK protein was detected by immunoblotting in metastatic melanomas but not in normal melanocytes. ECK mRNA levels tended to increase again during late melanoma progression. ECK and TIE mRNAs were also detected in highly metastatic variant cells but not in the corresponding poorly metastatic parental lines. Conversely, FES and KDR gene expression was lost in most advanced primary and metastatic melanomas. These findings suggest positive and negative roles for specific tyrosine kinases during progression.
...
PMID:Abnormal protein tyrosine kinase gene expression during melanoma progression and metastasis. 781 45

Basic fibroblast growth factor (b-FGF) appears to be an important positive modulator of the neointimal hyperplasia that occurs after prosthetic vascular graft implantation through its effects on vascular myointimal/smooth muscle cell migration and proliferation. The distribution and extent of b-FGF receptor (b-FGFR1) expression was compared using immunohistochemical techniques in normal porcine carotid arteries and at various times up to 6 weeks following implantation of small caliber prosthetic vascular grafts. At the time of graft harvest, specimens were infused with OCT medium at 100 mm Hg and rapidly frozen in liquid nitrogen. Transverse sections of the perianastomotic arterial tissues were labeled with primary mouse monoclonal antibody directed toward the extracellular domain of the receptor, followed by goat-anti mouse IgG and rabbit anti-goat IgG conjugated to horseradish peroxidase. The b-FGFR1-positive cells were identified by peroxidase activity within the Golgi complex of smooth muscle cells. Normal porcine carotid arteries showed no evidence of staining for b-FGFR1. However, at 6 weeks cells in the perianastomotic area clearly showed significant b-FGFR1 localization. Anti-muscle actin labeling confirmed these to be smooth muscle cells. The observed upregulation of b-FGFR1 expression supports the concept of positive feedback by cytokines as a contributing factor to the hyperplastic response of smooth muscle cells after prosthetic vascular graft implantation. This finding further supports a potential strategy to specifically target activated smooth muscle cells through use of mitotoxin therapy.
...
PMID:Upregulation of b-FGF receptor expression after carotid bypass. 783 Apr 2


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---