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 region between DXS52 and Factor VIII gene in the human Xq28 chromosomal band contains a G+C-rich isochore to which many genes have been mapped. We report here the isolation and characterization of a transcript mapping about 50 kb telomeric from the vasopressin type 2 receptor gene in a 180-kb YACs/cosmid contig containing the L1CAM gene at its centromeric end. The determined transcribed sequence from a human fetal brain library is identical to that of the recently identified accessory protein HCFC1 (host cell factor, also called C1) that activates herpes simplex virus VP16 (alpha TIF) transactivator protein for association with the octamer motif-binding protein Oct-1 (Cell 74: 115, 1993). The gene is expressed in a ubiquitous pattern and a larger transcript of approximately 10 kb is present in all the tissues tested, while an alternatively spliced RNA of approximately 8.0 kb is present in muscle and heart tissues. Genomic sequencing allowed us to determine that the sequenced transcript is assembled from 26 exons spread over a relatively small genomic region of approximately 24 kb. This alllowed us to determine that a previously reported cDNA clone arises from the splicing out of an internal portion of exon 8 which does not change the reading frame. All together these results raise the possibility that alternative mRNA processing could partly contribute to the diversity of the polypeptide HCFC1 family in a subset of tissues.
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PMID:Genomic organization of the human VP16 accessory protein, a housekeeping gene (HCFC1) mapping to Xq28. 782 97

The FMS proto-oncogene encodes a polypeptide growth factor receptor expressed on the cell surface of monocytes and B lymphocytes within the haematological system. Mutations of the FMS gene at codons 301 and 969 have been detected in a number of haematological disorders. Mutations at these codons are thought to be important in the pathogenesis of leukaemia in cells expressing a mutant receptor. Following our finding that the colony stimulating factor-1 receptor (CSF-1R) was expressed on B cells, we have assessed DNA from 17 patients with B-cell chronic lymphocytic leukaemia (CLL), 15 with acute lymphoblastic leukaemias (ALL), two samples from patients with B-cell non-Hodgkin's lymphoma (B-NHL), and 20 haematologically normal individuals for the presence of C-terminal mutations of the FMS gene. Using single stranded conformational polymorphism analysis (SSCP), a single band shift was detected resulting from a nucleotide insertion at codon 965 in the DNA isolated from a patient with B-NHL. These results indicate that mutations of the FMS gene in this region are rare in B-cell malignancy but may contribute to the pathogenesis of leukaemias and lymphomas in a small subset of patients. However, the presence of other mutations not detected using this type of analysis cannot be excluded.
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PMID:A C-terminal FMS mutation in a patient with B-cell malignancy. 784 11

The alpha/immediate early genes of herpes simplex virus are regulated by the specific assembly of a multiprotein enhancer complex containing the Oct-1 POU domain protein, the viral alpha-transinduction factor alpha TIF, (VP16, ICP25), and the C1 cellular factor. The C1 factor from mammalian cells is a heterogeneous but related set of polypeptides that interact directly with the alpha-transinduction factor to form a heteromeric protein complex. The isolation of cDNAs encoding the polypeptides of the C1 factor suggests that these proteins are proteolytic products of a novel precursor. The sequence of the amino termini of these polypeptide products indicate that the proteins are generated by site-specific cleavages within a reiterated 20-amino acid sequence. Although the C1 factor appears to be ubiquitously expressed, it is localized to subnuclear structures in specific cell types.
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PMID:The cellular C1 factor of the herpes simplex virus enhancer complex is a family of polypeptides. 787 3

The yeast assimilatory sulfate reductase is a complex enzyme that is responsible for conversion of sulfite into sulfide. To obtain information on the nature of this enzyme, we isolated and sequenced the MET10 gene of Saccharomyces cerevisiae and a divergent MET10 allele from Saccharomyces carlsbergensis. The polypeptides deduced from the identically sized open reading frames (1,035 amino acids) of both MET10 genes have molecular masses of around 115 kDa and are 88% identical to each other. The transcript of S. cerevisiae MET10 has a size comparable to that of the open reading frame and is transcriptionally repressed by methionine in a way similar to that seen for other MET genes of S. cerevisiae. Distinct homology was found between the putative MET10-encoded polypeptide and flavin-interacting parts of the sulfite reductase flavoprotein subunit (encoded by cysJ) from Escherichia coli and several other flavoproteins. A significant N-terminal homology to pyruvate flavodoxin oxidoreductase (encoded by nifJ) from Klebsiella pneumoniae, together with a lack of obvious flavin mononucleotide-binding motifs in the MET10 deduced amino acid sequence, suggests that the yeast assimilatory sulfite reductase is a distinct type of sulfite reductase.
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PMID:Two divergent MET10 genes, one from Saccharomyces cerevisiae and one from Saccharomyces carlsbergensis, encode the alpha subunit of sulfite reductase and specify potential binding sites for FAD and NADPH. 792 66

Staphylococcus aureus strain D4508 is a toxic shock syndrome toxin 1-negative clinical isolate from a nonmenstrual case of toxic shock syndrome (TSS). In the present study, we have purified and characterized a new exotoxin from the extracellular products of this strain. This toxin was found to have a molecular mass of 25.14 kD by mass spectrometry and an isoelectric point of 5.65 by isoelectric focusing. We have also cloned and sequenced its corresponding genomic determinant. The DNA sequence encoding the mature protein was found to be 654 base pairs and is predicted to encode a polypeptide of 218 amino acids. The deduced protein contains an NH2-terminal sequence identical to that of the native protein. The calculated molecular weight (25.21 kD) of the recombinant mature protein is also consistent with that of the native molecules. When injected intravenously into rabbits, both the native and recombinant toxins induce an acute TSS-like illness characterized by high fever, hypotension, diarrhea, shock, and in some cases death, with classical histological findings of TSS. Furthermore, the activity of the toxin is specifically enhanced by low quantities of endotoxins. The toxicity can be blocked by rabbit immunoglobulin G antibody specific for the toxin. Western blotting and DNA sequencing data confirm that the protein is a unique staphylococcal exotoxin, yet shares significant sequence homology with known staphylococcal enterotoxins, especially the SEA, SED, and SEE toxins. We conclude therefore that this 25-kD protein belongs to the staphylococcal enterotoxin gene family that is capable of inducing a TSS-like illness in rabbits.
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PMID:Characterization and biological properties of a new staphylococcal exotoxin. 796 53

Epidermal growth factor (EGF), a polypeptide with a potent mitogen activity, and its receptor [EGFR] have been previously identified in the kidney, but their expression in normal and diseased kidneys has not been fully elucidated. In order to evaluate EGFR in various histological types of renal injury, EGFR expression was studied by the immunohistochemical avidin-biotin complex (ABC) method with a monoclonal antibody EGFR1 on paraffin sections from 10 normal kidneys, 56 renal biopsies with various types of glomerulonephritis (GN), and 20 renal grafts with rejection. EGFR expression was observed in (a) 3 of 10 (30%) normal kidneys, (b) 17 of 39 (43.6%) renal biopsies with various types of GN mainly in membranous GN (57%) and in focal segmental glomerulosclerosis (FSG) (62.5%), (c) 6 of 17 (35.3%) biopsies with various types of systemic lupus erythematosus GN, and (d) 12 of 20 (60%) renal grafts with acute (42.9%) and chronic (69.2%) rejection. EGFR was mainly localized to the epithelial cells of the distal and collecting tubules and extraglomelar vessels, while it was observed less frequently in parietal epithelial cells and along glomerular basement membranes. Notably EGFR was detected in the epithelial cells adjacent to adhesions with Bowman's capsule and in the connective tissue of fibrocellular crescents. In conclusion, EGFR expression was observed more frequently in diseased than in normal kidneys. The increased incidence of EGFR expression in FSG, in chronic rejection, in small adhesions with Bowman's capsule and fibrocellular crescents suggest that EGF/EGFR may be correlated with a disturbed extracellular matrix production resulting in formation of early sclerotic lesions.
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PMID:Immunohistochemical study of epidermal growth factor receptor (EGFR) in various types of renal injury. 797 Jan 18

Bradykinin activates adenylate cyclase via a pathway that involves the 'up-stream' regulation of phospholipase D (PLD)-catalysed hydrolysis of phosphatidylcholine and activation of protein kinase C (PKC) in airway smooth muscle [Stevens, Pyne, Grady and Pyne (1994) Biochem. J. 297, 233-239]. Coincident signal (Gs alpha and PKC) amplification of the cyclic AMP response can be completely attenuated either by diverting PLD-derived phosphatidate or by inhibiting PKC. In this regard, the coincident signal detector type II adenylate cyclase is expressed as a 110/112 kDa polypeptide in these cells. PKC alpha is not involved in the activation of adenylate cyclase, since a B2-receptor antagonist (NPC567, 10 microM) blocked its bradykinin-stimulated translocation to the membrane and was without effect against both bradykinin-stimulated PLD activity and cyclic AMP formation. Cyclic AMP formation can also be activated by platelet-derived growth factor (PDGF), via a PKC-dependent pathway, although the magnitude of the response is less than that elicited by bradykinin. Nevertheless, these results indicate that multiple receptor types employ PKC to initiate cyclic AMP signals. PDGF (10 ng/ml) elicited the marked sustained activation of extracellular-signal-regulated kinase-2 (ERK-2), whereas bradykinin (1 microM) provoked only modest transient activation of ERK-2. Deoxyadenosine (0.1 mM), a P-site inhibitor of adenylate cyclase, blocked bradykinin-stimulated cyclic AMP formation and converted the activation of ERK-2 into a sustained response. Thus the PKC-stimulated cyclic AMP response can limit the activation of ERK-2 in response to bradykinin. These studies indicate that the integration of distinct signal pathways by adenylate cyclase can determine the kinetics of ERK activation, an enzyme that appears to be important for mitogenic progression.
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PMID:Protein kinase C-dependent cyclic AMP formation in airway smooth muscle: the role of type II adenylate cyclase and the blockade of extracellular-signal-regulated kinase-2 (ERK-2) activation. 799 98

Intact bovine adrenal medullary chromaffin cells were preincubated with 32PO4, and the multiple-site phosphorylation of tyrosine hydroxylase (TH) was studied. Up to eight 32P-labeled peptides were produced by tryptic hydrolysis of TH; however, all of the tryptic phosphopeptides were derived from four phosphorylation sites--Ser8, Ser19, Ser31 and Ser40. In situ regulation of 32P incorporation into the latter three sites was demonstrated with a diverse set of pharmacological agents. 32P incorporation into Ser19 was preferentially increased by brief exposures to depolarizing secretagogues. Longer treatments also increased Ser31 and Ser40 phosphorylation. Nicotine, muscarine and vasoactive intestinal polypeptide--reflecting cholinergic and non-cholinergic components of sympatho-adrenal transmission--each produced different patterns of multiple-site phosphorylation of TH. Nicotine, bradykinin and histamine increased 32P incorporation at each of the three sites whereas muscarine, angiotensin II, endothelin III, prostaglandin E1, GABA and ATP selectively increased Ser31 phosphorylation. Nerve growth factor did not influence TH phosphorylation in chromaffin cells from adult adrenal glands but selectively increased Ser31 phosphorylation in chromaffin cells isolated from calf adrenal glands. 32P incorporation into Ser40 was selectively increased by forskolin and other cAMP-acting agents whereas vasoactive intestinal polypeptide increased Ser31 and Ser40 phosphorylation. Thus, the phosphorylation of TH in bovine chromaffin cells appears to be regulated at three sites by three separate intracellular signaling pathways--Ser19 via Ca2+/calmodulin-dependent protein kinase II; Ser31 via ERK (MAP2 kinases); and Ser40 via cAMP-dependent protein kinase. These signaling pathways, as well as the extracellular signals that were effective in stimulating them, are similar to those previously described for TH in rat pheochromocytoma cells. However, several of the pharmacological agents produced different patterns of multiple-site TH phosphorylation in the bovine chromaffin cells. These differences between tissues could be accounted for by differences in the coupling/access between the extracellular signal transduction systems and the intracellular signaling pathways as opposed to differences in the intracellular signaling pathways per se.
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PMID:Multiple signaling pathways in bovine chromaffin cells regulate tyrosine hydroxylase phosphorylation at Ser19, Ser31, and Ser40. 809 28

The beta gamma subunits (G beta gamma) of heterotrimeric G proteins modulate the activity of several signal-transducing effector molecules including G protein-coupled receptor kinases. G beta gamma binds to the carboxyl terminus of the beta-adrenergic receptor kinase (beta ARK) and regulates its activity. To investigate the effect of such a G beta gamma-binding domain on heterologous G beta gamma interactions, various receptors that can stimulate phospholipase C and/or type II adenylate cyclase were coexpressed in COS-7 cells with the carboxyl terminus of beta ARK1. Phosphoinositol hydrolysis in response to activation of receptors that stimulate phospholipase C via Gi beta gamma (alpha 2-adrenergic and M2-muscarinic cholinergic receptors) was markedly inhibited by the coexpressed beta ARK1 polypeptide, whereas that mediated by Gq alpha subunits (alpha 1-adrenergic and M1-muscarinic cholinergic receptors) was unaffected. Increased cellular cAMP levels due to stimulation of receptors and coexpressed adenylate cyclase II displayed marked inhibition in the presence of the beta ARK1 polypeptide. Moreover, inhibition of adenylate cyclase produced by alpha 2-adrenergic receptor stimulation (a Gi alpha-mediated process) was unaffected, indicating that the beta ARK1 polypeptide provides a useful tool for distinguishing between G alpha and G beta gamma pathways.
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PMID:Cellular expression of the carboxyl terminus of a G protein-coupled receptor kinase attenuates G beta gamma-mediated signaling. 811 63

Transforming growth factor beta (TGF-beta) is a multifunctional polypeptide that regulates the proliferation and differentiation of various cells and has an angiogenic effect in vivo, although it inhibits the growth of cultured endothelial cells. We report here that TGF-beta treatment of quiescent cultures of mouse embryo-derived AKR-2B cells, which are growth-stimulated by TGF-beta, and human lung adenocarcinoma A549 cells, which are growth-inhibited by TGF-beta, results in the induction of vascular endothelial growth factor (VEGF) mRNA and protein. Maximal VEGF mRNA levels occurred 4-8 h after stimulation with a decline to background levels in 24 h. In contrast, the related placenta growth factor mRNA was not induced by TGF-beta in these cells. No VEGF receptor mRNA was seen in AKR-2B cells. Also, TGF-beta treatment of endothelial cells, which express the FLT1 and KDR/FLK-1 receptors for VEGF, did not cause VEGF induction. Because VEGF is known to be a strong angiogenic factor for endothelial cells, the results suggest that the angiogenic effect of TGF-beta on endothelial cells in blood vessels may be mediated at least partly by a paracrine induction of VEGF in other surrounding cell types.
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PMID:Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells. 811 73


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