Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
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.
 ...
PMID:Regulation of platelet-derived growth factor receptor expression by cell context overrides regulation by cytokines. 884 29

Hair follicles develop and are maintained by multiple rounds of inductive events involving interactions among various cell types within the follicles and the adjacent mesenchyme. Although evidence suggests that several growth factors, cell adhesion molecules, and transcriptional regulators are involved in those cell-cell interactions, the molecular mechanisms regulating each pivotal step of hair follicle development, such as formation of the hair germ, root sheath, sebaceous gland, and hair canal, remain largely unknown. In this study, we established the antagonistic monoclonal antibody APA5 against platelet-derived growth factor (PDGF) receptor-alpha (PDGFR-alpha) and used it to investigate the role of PDGFR-alpha in neonatal skin development. In addition to the dermal mesenchyme, a known site of PDGFR-alpha expression, immunohistologic staining of neonatal skin detected transient expression of PDGFR-alpha in the perinatal epidermis for several days. On the other hand, ligands for PDGFR-alpha were detected in epithelial cells and sebaceous glands of hair follicles. To determine whether this contiguous expression of PDGF and PDGFR-alpha in neonatal skin plays a functional role, we injected APA5 into neonates to block the function of PDGFR-alpha. Consistent with the PDGF/PDGFR-alpha expression in the neonatal skin, two defects were induced by this procedure. First, hair canal formation in the epidermis was severely suppressed. Second, the growth of dermal connective tissues and of hair follicles of pelage hairs was suppressed. These results indicate that PDGF signals are involved in both the epidermis-follicle interaction and the dermal mesenchyme-follicle interaction required for hair canal formation and the growth of the dermal mesenchyme, respectively.
 ...
PMID:Involvement of platelet-derived growth factor receptor-alpha in hair canal formation. 887 46

1. Platelet-derived growth factor (PDGF) plays an important role not only in mesenchyme-derived tissues, but also in the mammalian central nervous system. The Patch mutant (Ph/+) lacks one copy of the PDGFR-alpha gene. However, it is not clear whether there are differences in expression of PDGF receptor alpha-subunit (PDGFR-alpha) in brain tissue of the Patch heterozygous (Ph/+) mutants compared to wild-type C57Bl (+/+) mice. 2. The level of PDGRF-alpha mRNA expression is slightly lower in Patch mutant than in normal littermate. 3. Protein and total RNA isolated from mouse brain tissue and primary type 1 astrocyte cultures were studied with Western and Northern blotting techniques. There was no measurable difference ir PDGFR-alpha protein expression between the Patch and wild-type mouse nervous system. Adjustment of transcriptional efficiency and messenger stability may contribute to this phenomenon, whose biological significance remains unclear. 4. Further, the expression of PDGRF-alpha protein and message in mouse brain tissues is developmentally regulated. Its level remains high during the embryonic period and declines below measurable levels in adult.
 ...
PMID:Expression of platelet-derived growth factor (PDGF) receptor alpha-subunit in mouse brain: comparison of Patch mutants and normal littermates. 887 50

The platelet-derived growth factor receptor alpha subunit (PDGFR alpha) is expressed by glial precursors, glial cells, and some peripheral neurons during normal rodent development. Its ligands are expressed ubiquitously in neurons, including sensory and motor neurons. Thus, neuronally secreted PDGF-A may play a paracrine role in the development of both glial cells and peripheral neurons. The Patch (Ph) mutation, which is a deletion of the PDGFR alpha, is a homozygous embryonic lethal mutation in the mouse. Previously, several developmental abnormalities, including deficiencies in connective tissues in many organs, aberrant neural crest cell migration, and defects in non-neuronal derivatives of crest cells, have been shown to be associated with the Patch mutation. However, whether and the extent to which motor and sensory neurons are affected by the mutation are not known. Here, we have examined the survival and/or morphological differentiation of spinal motor and sensory (dorsal root ganglion) neurons during the period of naturally occurring cell death, i.e., between E14 and E18, in control and Ph/Ph mice. The results show a 65-70% decrease in motor and sensory neuron numbers in Ph/Ph mice, compared to controls, at all stages examined. Furthermore, motoneurons in Ph/Ph mice were significantly smaller than those in controls. Because of the bidirectional nature of neuron-glial cell interactions, these results suggest that PDGFR alpha plays an important role in glial cell development and, thus, indirectly in neuronal cell development or, alternatively, that PDGF and the PDGFR alpha are directly involved in peripheral neuron survival and development by an autocrine/paracrine mechanism.
 ...
PMID:Altered development of spinal cord in the mouse mutant (Patch) lacking the PDGF receptor alpha-subunit gene. 892 82

We have cloned and sequenced the teleost homologs of the human genes encoding platelet-derived growth factor receptor-beta (PDGFR beta) and macrophage colony-stimulating factor 1 receptor (CSFIR) from the puffer fish Fugu rubripes. The Fugu PDGFR beta and CSFIR genes each consist of 21 coding exons similar to the human CSFI gene, but are considerably smaller than their human counterparts because of the smaller introns. Furthermore, the two Fugu genes are linked tandemly in a head-to-tail array similar to their human homologs with 2.2 kb of intergenic sequence. Amino acid sequences of the Fugu and human PDGFR beta and CSFIR genes show an overall homology of 45% and 39%, respectively, with the kinase domains showing a much higher degree of conservation. Dot-matrix analysis revealed several short stretches of conserved sequences in the 3' untranslated regions of the PDGFR beta genes and the adjacent promoter regions of the CSFIR genes. These conserved sequences may have a role in the regulation of expression of either or both of these closely linked genes.
 ...
PMID:Conserved linkage between the puffer fish (Fugu rubripes) and human genes for platelet-derived growth factor receptor and macrophage colony-stimulating factor receptor. 897 13

Astrocytes invade the developing retina from the optic nerve head, over the axons of retinal ganglion cells (RGCs). RGCs express the platelet-derived growth factor A-chain (PDGF-A) and retinal astrocytes the PDGF alpha-receptor (PDGFR alpha), suggesting that PDGF mediates a paracrine interaction between these cells. To test this, we inhibited PDGF signaling in the eye with a neutralizing anti-PDGFR alpha antibody or a soluble extracellular fragment of PDGFR alpha. These treatments inhibited development of the astrocyte network. We also generated transgenic mice that overexpress PDGF-A in RGCs. This resulted in hyperproliferation of astrocytes, which in turn induced excessive vasculogenesis. Thus, PDGF appears to be a link in the chain of cell-cell interactions responsible for matching numbers of neurons, astrocytes, and blood vessels during retinal development.
 ...
PMID:PDGF mediates a neuron-astrocyte interaction in the developing retina. 898 60

The profile of fibrogenic growth factor expression was assessed in biopsies from 27 patients with IgA nephropathy (IgAN), 14 focal and segmental glomerulsclerosis (FSGS) patients and 8 controls, by immunohistochemistry. Increased platelet-derived growth factor (PDGF)-A and PDGF-B expression was detected in glomeruli and in vascular structures and collapsed tubules in the interstitium. Computer assisted image analysis demonstrated increased glomerular PDGF-A in IgAN (P < 0.05), but not FSGS patients, compared to controls, suggesting an association with mesangial proliferation. PDGF receptors were prominent in areas of mesangial expansion and intertubular fibrosis. Significant increases in interstitial PDGF Receptor beta (PDGFR-beta) were detected for both IgAN (P < 0.01) and FSGS (P < 0.05) patients. Interstitial PDGFR-beta expression was significantly correlated to monocyte/macrophage infiltrate (P < 0.0001). Increased basic fibroblast growth factor (bFGF) expression was observed segmentally in glomeruli, and in areas of tubulointerstitial damage. Higher proportions of patients with FSGS than IgAN had elevated interstitial bFGF (P < 0.005) and PDGF, reflecting the more severe degree of vascular and tubulointerstitial injury in FSGS patients. This study demonstrates distinct patterns of fibrinogenic growth factors in IgAN and FSGS, strongly associated with the severity and type of injury.
 ...
PMID:Altered expression of fibrogenic growth factors in IgA nephropathy and focal and segmental glomerulosclerosis. 899 34

TEL is a novel member of the ETS family of transcriptional regulators which is frequently involved in human leukemias as the result of specific chromosomal translocations. We show here by co-immunoprecipitation and GST chromatography analyses that TEL and TEL-derived fusion proteins form homotypic oligomers in vitro and in vivo. Deletion mutagenesis identifies the TEL oligomerization domain as a 65 amino acid region which is conserved in a subset of the ETS proteins including ETS-1, ETS-2, FLI-1, ERG-2 and GABP alpha in vertebrates and PNTP2, YAN and ELG in Drosophila. TEL-induced oligomerization is shown to be essential for the constitutive activation of the protein kinase activity and mitogenic properties of TEL-platelet derived growth factor receptor beta (PDGFR beta), a fusion oncoprotein characteristic of the leukemic cells of chronic myelomonocytic leukemia harboring a t(5;12) chromosomal translocation. Swapping experiments in which the TEL oligomerization domain was exchanged by the homologous domains of representative vertebrate ETS proteins including ETS-1, ERG-2 and GABP alpha show that oligomerization is a specific property of the TEL amino-terminal conserved domain. These results indicate that the amino-terminal domain conserved in a subset of the ETS proteins has evolved to generate a specialized protein-protein interaction interface which is likely to be an important determinant of their specificity as transcriptional regulators.
 ...
PMID:A domain of TEL conserved in a subset of ETS proteins defines a specific oligomerization interface essential to the mitogenic properties of the TEL-PDGFR beta oncoprotein. 900 69

Platelet-derived growth factor alpha-receptors (PDGFR alpha) are expressed by a subset of neuroepithelial cells in the ventral half of the embryonic day 14 (E14) rat spinal cord. The progeny of these cells subsequently proliferate and migrate into the dorsal parts of the cord after E16. Here, we show that E14 ventral cells are able to generate oligodendrocytes in culture but that dorsal cells acquire this ability only after E16, coinciding with the appearance of PDGFR alpha-immunoreactive cells in the starting population. PDGFR alpha-positive cells in optic nerve and spinal cord cultures co-labelled with antibody markers of oligodendrocyte progenitors. When PDGFR alpha-positive cells were purified from embryonic rat spinal cords by immunoselection and cultured in defined medium, they all differentiated into oligodendrocytes. Very few oligodendrocytes developed in cultures of embryonic spinal cord cells that had been depleted of PDGFR alpha-expressing cells by antibody-mediated complement lysis. These data demonstrate that all PDGFR alpha-positive cells in the embryonic rat spinal cord are oligodendrocyte progenitors and that most or all early-developing oligodendrocytes are derived from these ventrally-derived precursors.
 ...
PMID:Spinal cord oligodendrocytes develop from ventrally derived progenitor cells that express PDGF alpha-receptors. 901 28


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