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Domain Receptor (domain + receptor)

Distribution by Scientific Domains

Medical Sciences	53%
Life Sciences	38%

Kinds of Domain Receptor

discoidin domain receptor

Selected Abstracts

Upregulation of discoidin domain receptor 2 in nasopharyngeal carcinoma,

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2008
Huey-Huey Chua PhD
Abstract Background. Nasopharyngeal carcinoma (NPC) is associated with Epstein-Barr virus (EBV) and has high metastatic potential. Discoidin domain receptors (DDR1, DDR2) are receptor-type tyrosine kinases activated by collagen. Their ability to induce expression of matrix metalloproteinase is related with tumor invasion. Therefore, we aim to investigate DDRs gene expression and its regulation in NPC. Methods and Results. By use of real-time quantitative polymerase chain reaction (Q-PCR), DDR2 gene expression but not DDR1 was significantly higher in primary and metastatic NPC. DDR2 was predominantly distributed in NPC tumor cells rather than in infiltrating lymphocytes. EBV Z-transactivator (Zta) transfection may distinctly elevate DDR2 level. Furthermore, data from reporter assay indicate that Zta could transactivate DDR2 promoter activity, suggesting the possible upregulation mechanism. Conclusion. DDR2 was differentially upregulated in NPC and modulated by EBV Zta protein. DDR2 may play a role in NPC invasion and serve as a diagnostic and therapeutic target. © 2007 Wiley Periodicals, Inc. Head Neck, 2008 [source]

Regulation of chondrocyte differentiation by the actin cytoskeleton and adhesive interactions

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2007
Anita Woods
Chondrocyte differentiation is a multi-step process characterized by successive changes in cell morphology and gene expression. In addition to tight regulation by numerous soluble factors, these processes are controlled by adhesive events. During the early phase of the chondrocyte life cycle, cell,cell adhesion through molecules such as N-cadherin and neural cell adhesion molecule (N-CAM) is required for differentiation of mesenchymal precursor cells to chondrocytes. At later stages, for example in growth plate chondrocytes, adhesion signaling from extracellular matrix (ECM) proteins through integrins and other ECM receptors such as the discoidin domain receptor (DDR) 2 (a collagen receptor) and Annexin V is necessary for normal chondrocyte proliferation and hypertrophy. Cell,matrix interactions are also important for chondrogenesis, for example through the activity of CD44, a receptor for Hyaluronan and collagens. The roles of several signaling molecules involved in adhesive signaling, such as integrin-linked kinase (ILK) and Rho GTPases, during chondrocyte differentiation are beginning to be understood, and the actin cytoskeleton has been identified as a common target of these adhesive pathways. Complete elucidation of the pathways connecting adhesion receptors to downstream effectors and the mechanisms integrating adhesion signaling with growth factor- and hormone-induced pathways is required for a better understanding of physiological and pathological skeletal development. J. Cell. Physiol. 213: 1,8, 2007. © 2007 Wiley-Liss, Inc. [source]

Discoidin domain receptor 1 mediates collagen-induced inflammatory activation of microglia in culture

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2008
Min-Chul Seo
Abstract Discoidin domain receptor 1 (DDR1) is a nonintegrin collagen receptor tyrosine kinase with an extracellular domain homologous to discoidin 1 of a soil-living amoeba Dictyostelium discoideum. We have previously demonstrated that DDR1 mediates collagen-induced nitric oxide production in J774A.1 murine macrophages. Because collagen is one of the main components of extracellular matrix in the central nervous system, we hypothesized that collagen also induces inflammatory activation of brain microglia, and DDR1 may mediate collagen-induced microglial activation. Using BV-2 mouse microglial cells and mouse primary microglial cultures, we have demonstrated that (1) collagen induces inflammatory activation of microglia as evidenced by production of nitric oxide, expression of inducible nitric oxide synthase, COX-2, CD40, and matrix metalloproteinase,9; (2) DDR1 is expressed in microglia and is phosphorylated by collagen treatment; and (3) collagen-induced microglial activation is abrogated by DDR1 blockade but not by integrin neutralization. We have further shown that p38 MAPK, c-Jun N-terminal kinase, and nuclear factor,kappa B are involved in the collagen-DDR1-induced microglial activation. Our results suggest that collagen can induce inflammatory activation of brain microglia and that DDR1 mediates this effect of collagen in an integrin-independent manner. © 2007 Wiley-Liss, Inc. [source]

Cell-mediated Delivery and Targeted Erosion of Vascular Endothelial Growth Factor-Crosslinked Hydrogels

MACROMOLECULAR RAPID COMMUNICATIONS, Issue 14 2010
Sung Hye Kim
Abstract We have previously reported a novel polymeric delivery vehicle that is assembled via interaction between heparin and the vascular endothelial growth factor (VEGF). Here, the cell-responsiveness of this hydrogel,including the delivery of VEGF in response to VEGFR-2 overexpressing PAE/KDR cells (porcine aortic endothelial cells (PAE) equipped with the transcript for the kinase insert domain receptor (KDR)), consequent erosion of the hydrogel matrix, and cellular response,are highlighted. The release of VEGF and hydrogel erosion reached 100% only in the presence of PAE/KDR. The [PEG-LMWH/VEGF] hydrogel (PEG,=,poly(ethylene glycol), LMWH,=,low molecular weight heparin) correspondingly prompted increases in VEGFR-2 phosphorylation and proliferation of PAE/KDR cells. This study proves that growth factor-crosslinked hydrogels can liberate VEGF in response to specific receptors, causing gel erosion and desired cell responses. The promise of these approaches in therapeutic applications, including targeted delivery, is suggested. [source]

Molecular Reproduction & Development: Volume 77, Issue 1

MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 1 2010
Article first published online: 17 NOV 200
Leydig cells in the seminiferous tubule co-express the lutenizing hormone receptor (LHR; red) and the discoidin domain receptor 2 (DDRs; green). Together, these receptors help maintain production of testosterone, which in turn regulates spermatogenesis. Kano et al. (page 29 in this issue) describe the effects of the loss of DDR2 on testicular function in mice. [source]

Discoidin domain receptor 2 mediates the collagen II-dependent release of interleukin-6 in primary human chondrocytes,

THE JOURNAL OF PATHOLOGY, Issue 2 2009
Andreas R Klatt
Abstract We deciphered constituent parts of a signal transduction cascade that is initiated by collagen II and results in the release of various pro-inflammatory cytokines, including interleukin-6 (IL-6), in primary human chondrocytes. This cascade represents a feed-forward mechanism whereby cartilage matrix degradation is exacerbated by the mutually inducing effect of released collagen II fragments and pro-inflammatory cytokines. We previously proposed discoidin domain receptor 2 as a central mediator in this event. Since this cascade plays a prominent role in the pathogenesis of osteoarthritis, our study further investigates the hypothesis that discoidin domain receptor 2 is a candidate receptor for collagen II, and that transcription factor NF,B, lipid kinase PI3K, and the MAP kinases are constituent parts of this very signal transduction cascade. To accomplish this, we selectively knocked down the molecules of interest in primary human chondrocytes, induced the specified cascade by incubating primary human chondrocytes with collagen II, and observed the outcome, specifically the changes in interleukin-6 release. Knockdown was performed by siRNA-mediated gene silencing in the case of discoidin domain receptor 2 (DDR2) or by using specific inhibitors for the remainder of the molecules. Results indicated that discoidin domain receptor 2 mediates the collagen II-dependent release of interleukin-6 in primary human chondrocytes and that MAP kinases p38, JNK and ERK, as well as transcription factor NF,B, are integral components of intracellular collagen II signalling. Given the detrimental role of these molecules in osteoarthritis, our findings provide new targets for more specific therapeutics, which may have fewer side effects than those currently applied. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Attenuation of osteoarthritis progression by reduction of discoidin domain receptor 2 in mice

ARTHRITIS & RHEUMATISM, Issue 9 2010
Lin Xu
Objective To investigate whether the reduction of discoidin domain receptor 2 (DDR-2), a cell membrane tyrosine kinase receptor for native type II collagen, attenuates the progression of articular cartilage degeneration in mouse models of osteoarthritis (OA). Methods Double-heterozygous (type XI collagen,deficient [Col11a1+/,] and Ddr2 -deficient [Ddr2+/,]) mutant mice were generated. Knee joints of Ddr2+/, mice were subjected to microsurgical destabilization of the medial meniscus. Conditions of the articular cartilage from the knee joints of the double-heterozygous mutant and surgically treated mice were examined by histology, evaluated using a modified Mankin scoring system, and characterized by immunohistochemistry. Results The rate of progressive degeneration in knee joints was dramatically reduced in the double-heterozygous mutant mice compared with that in the type XI collagen,deficient mice. The progression in the double-heterozygous mutant mice was delayed by ,6 months. Following surgical destabilization of the medial meniscus, the progressive degeneration toward OA was dramatically delayed in the Ddr2+/, mice compared with that in their wild-type littermates. The articular cartilage damage present in the knee joints of the mice was directly correlated with the expression profiles of DDR-2 and matrix metalloproteinase 13. Conclusion Reduction of DDR-2 expression attenuates the articular cartilage degeneration of knee joints induced either by type XI collagen deficiency or by surgical destabilization of the medial meniscus. [source]

Upregulation of discoidin domain receptor 2 in nasopharyngeal carcinoma,

Characterization of an Antibody to the Human Melatonin mt1 Receptor

JOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2001
L. M. Williams
Abstract Melatonin acts via high affinity, G-protein coupled, seven transmembrane domain receptors. To precisely localize these receptors, antibodies were raised in chickens against a 15 amino acid fragment at the intracellular C -terminal region of the human melatonin receptor subtype mt1 (DSSNDVADRVKWKPS, mt1338,352). A chimeric form of the receptor with a hydrophilic Flag peptide (DYKDDDDK) in sequence with the extracellular N -terminus (Flag-mt1) was generated by polymerase chain reaction and expressed in mammalian cell lines. An IgY antibody (Y31), which gave high antibody titres by enzyme-linked immunosorbent assay, was used to localize Flag-mt1 in stably transfected cells by immunofluoresence. Flag-mt1 localization with Y31 was identical to that obtained with the M5 antibody directed against the Flag epitope and was mainly localized to the Golgi apparatus with some staining at the cell surface. No staining was seen in untransfected cells with either antibody. Y31 staining was abolished using antibody preabsorbed with peptide antigen. Y31 immunofluorescence in fetal human kidney sections was restricted to nephrogenic regions and matched that of 2-(125I)iodomelatonin binding and mt1 gene expression by in situ hybridization. Y31 was used to immunoprecipitate biotinylated membrane proteins from Flag-mt1 stably transfected and untransfected CHO cells. Western blotting of immunoprecipitated proteins revealed two major bands specific to stably transfected cells, one at 63 kDa and one at 86 kDa. The first band almost certainly corresponds to the glycosylated form of Flag-mt1 and the second band to receptor dimers. Thus, Y31 antibody is suitable for use in detecting the human mt1 receptor subtype in tissues and in transfected cells. [source]

First cloning and functional characterization of a melatonin receptor in fish brain: a novel one?

JOURNAL OF PINEAL RESEARCH, Issue 2 2002
Pascaline Gaildrat
Melatonin, a neuroendocrine transducer of photoperiod, influences a number of physiological functions and behaviors through specific seven transmembrane domains receptors. We report here the first full-length cloning and functional characterization of a melatonin receptor (P2.6) in a fish, the pike (Teleost). P2.6 encodes a protein that is ,80% identical to melatonin receptors previously isolated partially in non-mammals and classified as members of the Mel1b subtype; but, it shares only 61% identity with the full-length human Mel1b melatonin receptor (hMT2). Expression of P2.6 results in ligand binding characteristics similar to that described for endogenous melatonin receptors. Selective antagonists of the hMT2 (4-phenyl-2-propionamidotetraline and luzindole) were poor competitors of 2-[125I]iodomelatonin binding to the recombinant receptor. In Chinese hamster ovary cells expressing both the cystic fibrosis transmembrane conductance regulator chloride channel and P2.6 receptor, melatonin counteracted the forskolin induced activation of the channel. The results are best explained by a selective inhibition of the adenylyl cyclase. By reverse transcription-polymerase chain reaction, P2.6 mRNA appeared expressed in the optic tectum and, to lesser extent, in the retina and pituitary. In conclusion, these results, together with those of a phylogenetic analysis, suggest that P2.6 might belong to a distinct subtype group within the vertebrate melatonin receptor family. [source]