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)

The expression and localization of PDGF beta receptors and PDGF-AB/BB in human healing wounds was evaluated by immunohistochemical techniques and in situ hybridization. Expression of PDGF beta receptor protein and PDGF-AB/BB were analyzed in wound margin biopsies using the PDGFR-B2 and PDGF 007 antibodies. PDGF beta receptor expression was minor in normal skin. An increased expression of PDGF beta receptor protein was prominent in vessels in the proliferating tissue zone in wounds as early as 1 d after surgery and was apparent < or = 4 wk after surgery. There was also a concordant increase in PDGF beta receptor mRNA detected by in situ hybridization. PDGF-AB/BB was present in healing wounds as well as in normal skin. In normal skin, expression of PDGF-AB/BB was confined to peripheral nerve fibers and to solitary cells of the epidermis and of the superficial dermis. In wounds, infiltrating mononuclear cells also stained for PDGF-AB/BB. To identify cell types expressing PDGF AB/BB and PDGF beta receptors, respectively, we performed double immunofluorescence stainings. PDGF beta receptors were expressed by vascular smooth muscle cells and cells in capillary walls; the receptor protein could not be detected in neurofilament containing structures, T lymphocytes, or CD68 expressing macrophages. PDGF-AB/BB colocalized with neurofilaments, it was present in Langerhans cells of the epidermis and in HLA-DR positive cells located in the epidermal/dermal junction area. Of the macrophages infiltrating the wound, 43 +/- 18% stained positively for PDGF AB/BB. Since PDGF-AB/BB and PDGF beta receptors are expressed in the healing wound, two essential prerequisites for a role of PDGF in wound healing are fulfilled.
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PMID:Tissue localization of beta receptors for platelet-derived growth factor and platelet-derived growth factor B chain during wound repair in humans. 848 74

The aim of this study was to examine platelet-derived growth factor alpha receptor (PDGFR-alpha) expression in gliomas of various degrees of malignancy and to correlate the findings with genetic alterations present in the same tumor samples. We analyzed 83 tumors by in situ hybridization using a PDGFR-alpha cRNA probe. Increased PDGFR-alpha mRNA expression was observed in astrocytic tumors of all stages of malignancy, although the highest levels were found in glioblastoma multiforme. To evaluate the frequency of PDGFR-alpha gene amplification, differential PCR requiring less DNA than Southern analysis was used with fluorescence-labeled primers corresponding to the kinase insert region of the PDGFR-alpha. Only 7 of 43 glioblastomas and none of the other tumors tested showed amplification of the PDGFR-alpha gene, suggesting that a mechanism other than gene amplification is responsible for the overexpression of PDGFR-alpha in glial brain tumors. Comparison of the in situ hybridization data with genetic alterations in the same tumor material showed a significant correlation of loss of heterozygosity on chromosome 17p (Fisher's exact, P < 0.0002) with high expression levels of PDGFR-alpha. Because that was the case in both low- and high-grade astrocytomas, our data imply that PDGFR-alpha is actively involved in tumor cell proliferation in early and late stages of glioma development. The association of PDGFR-alpha expression with a distinct subset of glioblastomas characterized by loss of heterozygosity 17p further supports the differentiation of these tumors into molecular variants.
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PMID:Association of loss of heterozygosity on chromosome 17p with high platelet-derived growth factor alpha receptor expression in human malignant gliomas. 854 59

A series of 3-indoleacrylonitrile tyrphostins, 2-chloro-3-phenylquinolines, and 3-arylquinoxalines were prepared and tested for inhibition of platelet-derived growth factor receptor tyrosine kinase (PDGF-RTK) activity. The potency of the inhibitors was found to be quinoxalines > quinolines > indoles. Lipophilic groups (methyl, methoxy) in the 6 and 7 positions and phenyl at the 3 position of quinoxalines and quinolines were essential for potency, in contrast to the hydrophilic catechol group in tyrphostins active against EGFR kinase inhibition at different sites. The inhibitors showed selectivity for PDGF and were not active against EGF receptor and HER-2/c-ErbB-2 receptor.
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PMID:Tyrphostins. 5. Potent inhibitors of platelet-derived growth factor receptor tyrosine kinase: structure-activity relationships in quinoxalines, quinolines, and indole tyrphostins. 866 60

Hematopoietic tyrosine kinase receptors (HGF-TKRs or class III TKRs) are essential for the growth and differentiation of hematopoietic cells. In this report we present a novel method that generates expression profiles of these receptors. The method was tested and optimized using the myeloblastic/ promyelocytic cell line KG1. The method involves PCR of cDNA using class III-specific degenerate primers and subsequent restriction enzyme digests of the 147 bp amplicons followed by fractionation on denaturing poly-acrylamide gels. This primary fingerprint of KG1 revealed equal expression of c-kit and flt3 and to a lesser extent PDGF-R alpha and c-fms. One residual band of unknown origin was seen and appeared to be the proto-oncogene RET following cloning and sequence analysis. This tyrosine kinase receptor is known to play an important role in neural development. In order to detect less abundantly expressed sequences, a secondary fingerprint was generated by pre-digestion of the receptors present in the primary expression profile and subsequent amplification of the residual band. No other tyrosine kinase receptors were observed in KG1. In conclusion, this method allows direct visualization of expression of the HGF-TKRs and has the potential to detect novel homologous receptors.
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PMID:Direct display of hematopoietic tyrosine kinase receptor expression profiles in KG1 cells by PCR using degenerate primers. 870 51

Immunohistochemical staining of 5 gliosarcomas was performed. Neoplastic glial component stained positive by GFAP. Endothelial cells lining the lumina of glomeruloid vascular structures stained positively with both UEA-1 and FVIII/RAg antibodies. Mesenchymal cells of sarcomatous areas stained positively with SMSA antibody and presence of PDGFR. The staining results demonstrate that the sarcomatous component of gliosarcoma is of smooth muscle origin and suggest that the vascular smooth muscle hyperplasia is related to PDGF.
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PMID:[Histopathological and immunohistochemical studies on gliosarcoma]. 876 32

Thymocytes not only receive signals from thymic epithelial cells but can also activate the latter, at least in the medulla. We have previously reported tyrosine phosphorylation of medullary epithelial cell substrates, after co-culture with thymocytes, and identified a number of protein tyrosine kinases in a line of thymic epithelial cells. We report here the in situ localisation by immunohistochemistry of JAK2 in medullary epithelial cells, of PDGF-R in medullary vascular endothelium, of FGF-R in Hassall's corpuscles, and the weak expression of JAK1 and RYK throughout the thymus.
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PMID:Expression of protein tyrosine kinases in the murine thymus stroma. 879 61

In order to obtain information about the developmental mechanisms of restenosis after angioplasty, we investigated an association between the expression of platelet-derived growth factors (PDGFs) and neointimal cell accumulation in rabbit femoral arteries subjected to balloon angioplasty. Northern analysis demonstrated that mRNA expression of PDGF B-chain (PDGF-B) increased markedly in the injured arteries, peaking at day 7 (sevenfold), and the transcripts remained augmented until day 21. Also transcripts of PDGF beta-receptor (PDGFR-beta) and alpha-receptor increased by 3- and 2.5-fold, respectively, but those of PDGF A-chain showed only a slight increase (1.5-fold). In situ hybridization and immunohistochemistry demonstrated the concordant expression of mRNA and protein for PDGF-B in the smooth muscle cells (SMCs) of injured vessels throughout the experiment. PDGF-B expression peaked in neointimal SMCs at day 7. In accordance with PDGF-B expression, cellular proliferation in neointima peaked at day 7, being followed by a dramatic increase of neointimal areas thereafter. Further, we demonstrated PDGFR-beta immunoreactivity in these neointimal cells with PDGF-B expression. Our data provide evidence that PDGF-B may stimulate vascular SMC proliferation and contribute to neointimal formation after angioplasty.
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PMID:Expression of platelet-derived growth factor B-chain in neointimal smooth muscle cells of balloon injured rabbit femoral arteries. 880 Apr 90

Oligodendrocyte responses in vitro to platelet-derived growth factor (PDGF) include proliferation, survival, migration, and changes in cell morphology and molecular expression. Studies of mixed glial cultures established that astrocytes secrete PDGF; thus astrocytes are considered to be key regulators of oligodendrocyte development in vitro. We previously demonstrated PDGF alpha receptor mRNA expression by oligodendrocyte progenitors and preoligodendrocytes during postnatal development of rat cerebral cortex. In the present study, we have mapped the spatial and temporal expression of PDGF A-chain ligand mRNA and alpha receptor mRNA to determine if the cell-cell interactions that form the basis for PDGF regulation of oligodendrocyte development in vitro are also present in vivo. By in situ hybridization (ISH) we demonstrate that at embryonic day 17 (E17) cells expressing receptor mRNA (PDGFR alpha +) are initially in the subventricular zone, at a distance from cells expressing ligand mRNA (PDGF+) in the cortical plate. By E20 PDGFR alpha + cells are found throughout the corpus callosum and cortical gray matter. PDGF+ cells are restricted to the cortical plate prenatally and only appeared in the corpus callosum postnatally. Combined immunocytochemistry and ISH demonstrated the PDGF+ cells colocalized with neurofilament, but not with GFAP. These data establish that PDGF is expressed by neurons during PDGFR alpha + oligodendrocyte progenitor migration from the subventricular zone to the corpus callosum and gray matter. Furthermore, neurons continue to express PDGF during the generation and differentiation of appropriate numbers of oligodendrocytes needed to myelinate axons as the nervous system matures.
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PMID:Evidence for neuronal regulation of oligodendrocyte development: cellular localization of platelet-derived growth factor alpha receptor and A-chain mRNA during cerebral cortex development in the rat. 881 10

We used Northern blot analysis to measure the expression of mRNA for platelet-derived growth factor subunit A (PDGF-A), PDGF-B and the PDGF-alpha receptor (PDGFR-alpha) and PDGF-beta receptor (PDGFR-beta) in ependymomas and medulloblastomas. We analyzed tissue from 5 patients for each tumor type, looking specifically for components of an autocrine or paracrine system in these tumors. PDGF-A was expressed in all tumors, PDGFR-alpha, which binds all 3 PDGF isoforms, was only found in ependymomas. Thus only ependymomas appeared to have a potential for using PDGFR-alpha autocrine loops. PDGF-B was expressed only in ependymomas, although the PDGFR-beta was expressed in both medulloblastomas and ependymomas. Again, therefore, only ependymomas appear to have a potential autocrine loop with PDGFR-beta. These data suggest that ependymomas have the biochemical prerequisites for autocrine and/or paracrine loops using PDGFR-alpha or PDGFR-beta systems. In this they resemble other glial tumors such as anaplastic astrocytomas and glioblastomas. Medulloblastomas do not appear to have the ligand and/or receptor for either the PDGFR-alpha or PDGFR-beta autocrine loop.
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PMID:Expression of platelet-derived growth factor transcripts in medulloblastomas and ependymomas. 884 Oct 77

Immunocytochemical data has indicated that platelet-derived growth factor receptor beta-subunit (PDGFR beta) expression by connective tissue cells is up-regulated in many disease states. To investigate potential causes of this up-regulation, we have evaluated conditions that regulate PDGF receptor transcript levels in cultured diploid human fibroblast model systems. We found combinations of soluble mediators and cell "context," which can regulate receptor transcripts (and receptor protein) over a 50-fold range, with cell context factors being far more potent regulators than soluble mediators. For cells grown under standard monolayer conditions on plastic, levels of both PDGFR beta and PDGFR alpha increase 10-fold as culture density increases. Cells grown in suspension or in three-dimensional gels express 10- to 20-fold higher transcript levels than cells plated on plastic at comparable density and serum concentration. The soluble mediators tested, including 14 cytokines and conditioned medium from activated lymphocytes, have only modest effects on transcript levels. Lymph decreases PDGFR beta transcript expression 4-fold, suggesting that a component of interstitial fluid contributes to maintenance of the low basal level of expression in normal tissues. The mitogenic responsiveness of cells cultured at different densities parallels the level of PDGFR beta expression. Blocking anti-PDGF receptor antibodies decrease receptor availability and mitogenic responsiveness in parallel. In both cases, the striking overlap between the PDGF-BB binding and mitogenesis dose-response curves suggests that the level of PDGF receptor expression can limit responsiveness to PDGF. Overall, these results suggest that the up-regulation of PDGF receptor expression seen under pathological conditions may be due to disruption of the cell's normal environment/context/cell shape/cell attachment and that this could serve to ensure that a proliferative response to PDGF would occur only under conditions in which there had been significant tissue damage.
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PMID:Regulation of platelet-derived growth factor receptor expression by cell context overrides regulation by cytokines. 884 29


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