Type 2 Fibroblast Growth Factor Receptor: A fibroblast growth factor receptor that is found in two isoforms. One receptor isoform is found in the MESENCHYME and is activated by FIBROBLAST GROWTH FACTOR 2. A second isoform of fibroblast growth factor receptor 2 is found mainly in EPITHELIAL CELLS and is activated by FIBROBLAST GROWTH FACTOR 7 and FIBROBLAST GROWTH FACTOR 10. Mutation of the gene for fibroblast growth factor receptor 2 can result in APERT SYNDROME.
The fibroblast growth factor receptor 2 gene is differentially spliced to encode two transmembrane tyrosine kinase receptor proteins that have different ligand-binding specificities and exclusive tissue distributions. We have used Cre-mediated excision to generate mice lacking the IIIb form of fibroblast growth factor receptor 2 whilst retaining expression of the IIIc form. Fibroblast growth factor receptor 2(IIIb) null mice are viable until birth, but have severe defects of the limbs, lung and anterior pituitary gland. The development of these structures appears to initiate, but then fails with the tissues undergoing extensive apoptosis. There are also developmental abnormalities of the salivary glands, inner ear, teeth and skin, as well as minor defects in skull formation. Our findings point to a key role for fibroblast growth factor receptor 2(IIIb) in mesenchymal-epithelial signalling during early organogenesis.. ...
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TY - JOUR. T1 - Coexpression of Truncated Human Cytomegalovirus gH with the UL115 Gene Product or the Truncated Human Fibroblast Growth Factor Receptor Results in Transport of gH to the Cell Surface. AU - Spaete, Richard R.. AU - Perot, Karen. AU - Scott, Patricia I.. AU - Nelson, Jay. AU - Stinski, Mark F.. AU - Pachl, Carol. PY - 1993/4. Y1 - 1993/4. N2 - The gH glycoprotein of herpesviruses is located on the cell surface in viral-infected cells but is retained in the endoplasmic reticulum (ER) when expressed separately from a recombinant expression vector. These observations suggested the requirement for either a viral function or a viral-induced cellular function which facilitates surface expression of gH, gL fulfills this role in the herpes simplex virus (HSV)-infected cell (J. Virol. 66, 2240-2250, 1992). We have identified the gene product of the UL115 open reading frame (ORF) as the functional homologue of HSV gL in the human cytomegalovirus (CMV) genome. In addition, we have ...
Fibroblast growth factor receptor (FGFR) is a receptor-type protein tyrosine kinase. Currently known FGFR mainly includes 4 types, namely FGFR1, FGFR2, FGFR3 and FGFR4. It has been clinically found that FGFR overexpression and activation of tumor tissues in a variety of cancers can promote tumor angiogenesis and tumor cell division and proliferation. Therefore, fibroblast growth factor receptors are widely regarded as an important class of anti-tumor drug targets, and have attracted widespread attention from pharmacists in various countries. In previous research, a binding gap in the ATP-binding domain of the FGFR1 protein was discovered, and a novel FGFR1 inhibitor design idea was proposed for the spatial structure of the gap.. Structure Fibroblast growth factor receptors consist of extracellular ligand domains that bind to fibroblast growth factor, which is the largest member of the growth factor ligand family, including 22 members. The extracellular ligand domain consists of three ...
definition of FGFR1K, what does FGFR1K mean?, meaning of FGFR1K, Fibroblast Growth Factor Receptor 1 Kinase, FGFR1K stands for Fibroblast Growth Factor Receptor 1 Kinase
This gene encodes a substrate for the fibroblast growth factor receptor. The encoded protein is found in the peripheral plasma membrane and links fibroblast growth factor receptor stimulation to activators of Ras. The encoded protein down-regulates extracellular regulated kinase 2 through direct binding. [provided by RefSeq, Jul 2013 ...
Shop Fibroblast growth factor receptor ELISA Kit, Recombinant Protein and Fibroblast growth factor receptor Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
Although drugable fibroblast growth factor receptor (FGFR) alterations in squamous cell carcinomas (SCC) of various entities are well known, little is known about FGFR modifications in squamous differentiated bladder cancer. Therefore, our study evaluated FGFR1-3 alterations as a putative therapeutic target in this subgroup. We analyzed 73 squamous differentiated bladder cancers (n = 10 pT2, n = 55 pT3, n = 8 pT4) for FGFR1-3 protein expression, FGFR1-3 copy number variations, FGFR3 chromosomal rearrangements (fluorescence in situ hybridization (FISH)) and FGFR3 mutations (SNapShot analysis). Only single cases displayed enhanced protein expression, most frequently FGFR3 overexpression (9.4% (6/64)). FISH showed no amplifications of FGFR1, 2 or 3. Break apart events were only slightly above the cut off in 12.1% (8/66) of cases and no FGFR3-TACC3 rearrangements could be proven by qPCR. FGFR3 mutations (p.S249C) were found in 8.5% (6/71) of tumors and were significantly associated with FGFR3 ...
TY - JOUR. T1 - Calcitriol downregulates fibroblast growth factor receptor 1 through histone deacetylase activation in HL-1 atrial myocytes. AU - Lee, Ting Wei. AU - Lee, Ting I.. AU - Lin, Yung Kuo. AU - Kao, Yu Hsun. AU - Chen, Yi Jen. PY - 2018/5/18. Y1 - 2018/5/18. N2 - Background: Fibroblast growth factor (FGF)-2 plays a crucial role in the pathophysiology of cardiovascular diseases (CVDs). FGF-2 was reported to induce cardiac hypertrophy through activation of FGF receptor 1 (FGFR1). Multiple laboratory findings indicate that calcitriol may be a potential treatment for CVDs. In this study, we attempted to investigate whether calcitriol regulates FGFR1 expression to modulate the effects of FGF-2 signaling in cardiac myocytes and explored the potential regulatory mechanism. Methods: Western blot, polymerase chain reaction, small interfering RNA, fluorometric activity assay, and chromatin immunoprecipitation (ChIP) analyses were used to evaluate FGFR1, FGFR2, FGFR3, FGFR4, phosphorylated ...
cansSAR 3D Structure of 6C1C | FGFR1 KINASE COMPLEX WITH INHIBITOR SN37116 | 6C1C_A | Fibroblast growth factor receptor 1 - Also known as FGFR1_HUMAN, FGFR1, BFGFR, CEK, FGFBR, FLG, FLT2, HBGFR. Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling
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.. ...
Alternative initiations of translation of the human fibroblast growth factor 2 (FGF-2) mRNA, at three CUG start codons and one AUG start codon, result in the synthesis of four isoforms of FGF-2. This process has important consequences on the fate of FGF-2: the CUG-initiated products are nuclear and their constitutive expression is able to induce cell immortalization, whereas the AUG-initiated product, mostly cytoplasmic, can generate cell transformation. Thus, the different isoforms probably have distinct targets in the cell. We show here that translation initiation of the FGF-2 mRNA breaks the rule of the cap-dependent ribosome scanning mechanism. First, translation of the FGF-2 mRNA was shown to be cap independent in vitro. This cap-independent translation required a sequence located between nucleotides (nt) 192 and 256 from the 5 end of the 318-nt-long 5 untranslated region. Second, expression of bicistronic vectors in COS-7 cells indicated that the FGF-2 mRNA is translated through a ...
FGFR (fibroblast growth factor receptor) signalling plays critical roles in embryogensis, adult physiology, tissue repair and many pathologies. Of particular interest over recent years, it has been implicated in a wide range of cancers, and concerted efforts are underway to target different aspects of FGFR signalling networks. A major focus has been identifying the canonical downstream signalling pathways in cancer cells, and these are now relatively well understood. In the present review, we focus on two distinct but emerging hot topics in FGF biology: its role in stromal cross-talk during cancer progression and the potential roles of FGFR signalling in the nucleus. These neglected areas are proving to be of great interest clinically and are intimately linked, at least in pancreatic cancer. The importance of the stroma in cancer is well accepted, both as a conduit/barrier for treatment and as a target in its own right. Nuclear receptors are less acknowledged as targets, largely due to ...
House, Stacey; Weinheimer, Carla; Kovac, Attila; Ornitz, David, "Endothelial-specific fibroblast growth factor receptor 1 and 2 deletion impairs vascular remodeling and recovery in an in vivo, closed-chest model of cardiac ischemia-reperfusion injury" (2012). Conference Abstracts and Posters. Paper 17. http://digitalcommons.wustl.edu/em_conf/17. ...
Background Fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in the development and function of multiple organs and organ systems, including the central nervous system (CNS). FGF signaling via FGFR1, one of the three FGFRs expressed in the CNS, stimulates proliferation of stem cells during prenatal and postnatal neurogenesis and participates in regulating cell-type ratios in many developing regions of the brain. Anomalies in FGFR1 signaling have been implicated in certain neuropsychiatric disorders. Fgfr1 expression has been shown, via in situ hybridization, to vary spatially and temporally throughout embryonic and postnatal development of the brain. However, in situ hybridization lacks sufficient resolution to identify which cell-types directly participate in FGF signaling. Furthermore, because antibodies raised against FGFR1 commonly cross-react with other members of the FGFR family, immunocytochemistry is not alone sufficient to accurately document Fgfr1 expression. Here, we
Background. Fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in the development and function of multiple organs and organ systems, including the central nervous system (CNS). FGF signaling via FGFR1, one of the three FGFRs expressed in the CNS, stimulates proliferation of stem cells during prenatal and postnatal neurogenesis and participates in regulating cell-type ratios in many developing regions of the brain. Anomalies in FGFR1 signaling have been implicated in certain neuropsychiatric disorders. Fgfr1 expression has been shown, via in situ hybridization, to vary spatially and temporally throughout embryonic and postnatal development of the brain. However, in situ hybridization lacks sufficient resolution to identify which cell-types directly participate in FGF signaling. Furthermore, because antibodies raised against FGFR1 commonly cross-react with other members of the FGFR family, immunocytochemistry is not alone sufficient to accurately document Fgfr1 expression. Here, we
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 ...
Recombinant protein of human fibroblast growth factor receptor 4 (FGFR4), transcript variant 2, 20 ug available for purchase from OriGene - Your Gene Company.
A constitutively active form of fibroblast growth factor 2 (FGFR2) was identified in rat osteosarcoma (ROS) cells by an expression cloning strategy. Unlike other tyrosine kinase receptors activated by N-terminal truncation in tumors, this receptor, FGFR2-ROS, contains an altered C terminus generated from chromosomal rearrangement with a novel gene, designated FGFR activating gene 1 (FRAG1). While the removal of the C terminus slightly activates FGFR2, the presence of the FRAG1 sequence drastically stimulates the transforming activity and autophosphorylation of the receptor. FGFR2-ROS is expressed as a unusually large protein and is highly phosphorylated in NIH 3T3 transfectants. FRAG1 is ubiquitously expressed and encodes a predicted protein of 28 kDa lacking significant structural similarity to known proteins. Epitope-tagged FRAG1 protein showed a perinuclear localization by immunofluorescence staining. The highly activated state of FGFR2-ROS appears to be attributed to constitutive dimer ...
AZD4547 is an orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR) with potential antineoplastic activity. FGFR inhibitor AZD4547 binds to and inhibits FGFR, which may result in the inhibition of FGFR-related signal transduction pathways, and, so, the inhibition of tumor cell proliferation and tumor cell death. FGFR, up-regulated in many tumor cell types, is a receptor tyrosine kinase essential to tumor cellular proliferation, differentiation and survival.
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2. Protein Tyrosine Kinase (PTK) family; Fibroblast Growth Factor Receptor 2 (FGFR2); catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FGFR2 is part of the FGFR subfamily, which are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of ...
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4. Protein Tyrosine Kinase (PTK) family; Fibroblast Growth Factor Receptor 4 (FGFR4); catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FGFR4 is part of the FGFR subfamily, which are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
As a promising target, FGFR4 is attracting intensive pharmaceutical and academic attention for developing novel target therapy against cancers driven by FGFR4
The KOMP Repository Collection is located at the MMRRC at the University of California, Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
Das Netzwerk Genomische Medizin (NGM) Lungenkrebs wurde im März 2010 von der Kölner Lungenkrebsgruppe (Lung Cancer Group Cologne) gegründet, um zunächst in Nordrhein-Westfalen eine umfassende und qualitativ hochwertige molekulare Diagnostik für alle Patienten mit Lungenkrebs anzubieten und so die Implementierung personalisierter Therapie in der klinischen Routineversorgung zu fördern. Mittlerweile agiert das NGM bundesweit und strebt eine Flächendeckung in Deutschland an.. ...
Product Name: Mouse mAb anti- human Fibroblast Growth Factor-basic (bFGF), Clone F-74Collection: AntibodySub Category: Monoclonal AntibodyImmunogen: Purified
CD334 / FGFR4 (fibroblast growth factor receptor 4), a transmembrane tyrosine kinase, which is expressed in many tissues, such as in lung, kidney, muscle, heart, pancreas, intestine and other, acts as a receptor for several fibroblast growth factors, namely FGF1, FGF2, FGF6, FGF8, and FGF19. Interaction with these growth factors initiates in cell the signaling cascades leading to the mitogenesis and cell differentiation. Presence of CD334 Gly338Arg allele correlates with prognostic parameters in various cancer studies. CD334 plays multiple roles in the organism, including those of muscle regeneration, cholesterol-to-bile acid metabolism, or glucose homeostasis ...
J:87411 Burns RC, Fairbanks TJ, Sala F, De Langhe S, Mailleux A, Thiery JP, Dickson C, Itoh N, Warburton D, Anderson KD, Bellusci S, Requirement for fibroblast growth factor 10 or fibroblast growth factor receptor 2-IIIb signaling for cecal development in mouse. Dev Biol. 2004 Jan 1;265(1):61-74 ...
The fibroblast growth factor receptors (FGFR) play essential roles both during development and in the adult. Upon ligand binding, FGFRs induce intracellular signaling networks that tightly regulate key biological processes, such as cell proliferation, survival, migration, and differentiation. Deregulation of FGFR signaling can thus alter tissue homeostasis and has been associated with several developmental syndromes as well as with many types of cancer. In human cancer, FGFRs have been found to be deregulated by multiple mechanisms, including aberrant expression, mutations, chromosomal rearrangements, and amplifications. In this review, we will give an overview of the main FGFR alterations described in human cancer to date and discuss their contribution to cancer progression. Mol Cancer Res; 8(11); 1439-52. ©2010 AACR. ...
FGF8 - FGF8 (untagged)-Human fibroblast growth factor 8 (androgen-induced) (FGF8), transcript variant B available for purchase from OriGene - Your Gene Company.
Recombinant human FGFR4 (460-end) was expressed by baculovirus in Sf9 cells using an N-terminal GST tag. FGFR4 is a member of the fibroblast growth factor receptor family, which play a role in mitogenesis and differentiation.
J:1618 Orr-Urtreger A, Givol D, Yayon A, Yarden Y, Lonai P, Developmental expression of two murine fibroblast growth factor receptors, flg and bek. Development. 1991 Dec;113(4):1419-34 ...
FGFR2 antibody (fibroblast growth factor receptor 2) for FACS, ICC/IF, IHC-P, WB. Anti-FGFR2 pAb (GTX25476) is tested in Human, Mouse samples. 100% Ab-Assurance.
FGFR2 antibody (fibroblast growth factor receptor 2) for ICC/IF, IHC-P, WB. Anti-FGFR2 pAb (GTX10648) is tested in Human samples. 100% Ab-Assurance.
Secher T, Novitskaia V, Berezin V, Bock E, Glenthøj B, Klementiev B. A neural cell adhesion molecule-derived fibroblast growth factor receptor agonist, the FGL-peptide, promotes early postnatal sensorimotor development and enhances social memory retention ...
CD332 / FGFR-2, 0.1 ml. The protein encoded by this gene is a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and throughout evolution.
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Looking for online definition of fibroblast growth factor receptor gene in the Medical Dictionary? fibroblast growth factor receptor gene explanation free. What is fibroblast growth factor receptor gene? Meaning of fibroblast growth factor receptor gene medical term. What does fibroblast growth factor receptor gene mean?
TY - JOUR. T1 - Fibroblast Growth Factor Receptor-3 Is Expressed in Undifferentiated Intestinal Epithelial Cells during Murine Crypt Morphogenesis. AU - Vidrich, Alda. AU - Buzan, Jenny M.. AU - Ilo, Chibuzo. AU - Bradley, Leigh. AU - Skaar, Kirstin. AU - Cohn, Steven. PY - 2004/5/1. Y1 - 2004/5/1. N2 - Prior studies have demonstrated that fibroblast growth factor receptor-3 (FGFR-3) regulates proliferation of undifferentiated intestinal epithelial cells in vitro. However, the function(s) of FGFR-3-mediated signaling during intestinal development and epithelial differentiation in vivo remain unknown. The goal of this study was to define the temporal, regional, and cell-specific patterns of FGFR-3 expression and its ligands during normal intestinal ontogeny and epithelial regeneration. Both the IIIb and IIIc isoforms of FGFR-3 mRNA, which result from differential splicing of the FGFR-3 primary transcript, were detected in mouse small intestine as early as embryonic day 16. FGFR-3 levels peaked in ...
Search and download thousands of Swedish university dissertations (essays). Full text. Free. Dissertation: Thyroid hormone mediates fibroblast growth factor receptor expression, which both alter cell surface mechanical properties of the mammalian cochlea.
Antibodies for proteins involved in fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development pathways, according to their Panther/Gene Ontology Classification
Growth and lineage-specific differentiation constitute crucial phases in the development of stem cells. Control over these processes is exerted by particular elements of the extracellular matrix, which ultimately trigger a cascade of signals that regulate uncommitted cells, by modulating their survival and cell cycle progression, to shape developmental processes. Uncontrolled, constitutive activation of fibroblast growth factor receptors (FGFR) results in bone abnormalities, underlining the stringent control over fibroblast growth factor (FGF) activity that must be maintained for normal osteogenesis to proceed. Mounting evidence suggests that FGF signalling, together with a large number of other growth and adhesive factors, is controlled by the extracellular glycosaminoglycan sugar, heparan sulfate (HS). In this review, we focus on FGF activity during osteogenesis, their receptors, and the use of HS as a therapeutic adjuvant for bone repair. © 2006 Elsevier B.V. All rights reserved ...
Cartilage degeneration driven by catabolic stimuli is a critical pathophysiological process in osteoarthritis (OA). We have defined fibroblast growth factor 2 (FGF-2) as a degenerative mediator in adult human articular chondrocytes. Biological effects mediated by FGF-2 include inhibition of proteoglycan production, up-regulation of matrix metalloproteinase-13 (MMP-13), and stimulation of other catabolic factors. In this study, we identified the specific receptor responsible for the catabolic functions of FGF-2, and established a pathophysiological connection between the FGF-2 receptor and OA. Primary human articular chondrocytes were cultured in monolayer (24 hours) or alginate beads (21 days), and stimulated with FGF-2 or FGF18, in the presence or absence of FGFR1 (FGF receptor 1) inhibitor. Proteoglycan accumulation and chondrocyte proliferation were assessed by dimethylmethylene blue (DMMB) assay and DNA assay, respectively. Expression of FGFRs (FGFR1 to FGFR4) was assessed by flow cytometry,
ADAMs (a disintegrin and metalloproteinase) have important roles in development and diseases such as cancer. Previously, an ADAM15 splice variant (ADAM15B), which contains an inserted cytoplasmic Src-binding site, was linked to clinical aggressiveness in breast cancer, yet little was known about how this splice variant affects the function of ADAM15. Here, we show that ADAM15B has enhanced catalytic activity in cell-based assays compared with ADAM15A, which lacks a Src-binding site, using shedding of fibroblast growth factor receptor 2iiib variant as an assay for catalytic activity. Moreover, the enhanced activity of ADAM15B compared with ADAM15A depends on Src because it is abolished by Src-kinase inhibitors and in Src(-/-) cells, but not in Src(-/-) cells rescued with Src. These findings provide insights into the mechanism of how a splice variant linked to clinical agressiveness in breast cancer causes increased activity of ADAM15B, and suggest that inhibitors of the ADAM15 protease activity or of the
A series of 2-oxo-3, 4-dihydropyrimido[4,5-d]-pyrimidinyl derivatives were designed and synthesized as new irreversible inhibitors of the FGFR family. One of the most promising compounds 2l potently inhibited FGFR1/2/3 with IC|sub|50|/sub| values of 1.06, 0.84 and 5.38 nM, respectively, whereas its …
Clinical use of recombinant fibroblast growth factor 21 (FGF21) for the treatment of type 2 diabetes and other disorders linked to obesity has been proposed; however, its clinical development has been challenging owing to its poor pharmacokinetics. Here, we describe an alternative antidiabetic strategy using agonistic anti-FGFR1 (FGF receptor 1) antibodies (R1MAbs) that mimic the metabolic effects of FGF21. A single injection of R1MAb into obese diabetic mice induced acute and sustained amelioration of hyperglycemia, along with marked improvement in hyperinsulinemia, hyperlipidemia, and hepatosteatosis. R1MAb activated the mitogen-activated protein kinase pathway in adipose tissues, but not in liver, and neither FGF21 nor R1MAb improved glucose clearance in lipoatrophic mice, which suggests that adipose tissues played a central role in the observed metabolic effects. In brown adipose tissues, both FGF21 and R1MAb induced phosphorylation of CREB (cyclic adenosine 5′-monophosphate response ...
Lab Rotation Projects Areas of interest; Molecular mechanisms by which members of the fibroblast growth factor (FGFs) and fibroblast growth factor receptor (FGFR) families, (produced by osteoblasts, osteoclasts and stromal cells) regulate bone development, remodeling and disorders of bone. Project 1- Fgf2 knockout and Fgf2 transgenic mice are utilized in loss and gain of function experiments to elucidate the role of FGF-2 in disorders of bone including osteoporosis. Project 2- Examination of the effects of cytokines and hormones including interleukin-1 (IL-1), parathyroid hormone (PTH), insulin-like growth factor-I (IGF-I), transforming growth factor beta (TGF?), prostaglandins (PGs) and glucocorticoids on FGF2 and FGFR signaling, gene transcription, mRNA stability and the activity of transfected Fgf2 promoter-luciferase reporter gene constructs.. ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.