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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A Schizosaccharomyces pombe homolog of mammalian genes encoding G protein beta subunits, gpb1+, was cloned by the polymerase chain reaction using primer pairs that correspond to sequences conserved in several G beta genes of other species followed by screening of genomic and cDNA libraries. The gpb1 gene encodes 317 amino acids that show 47% homology with human G beta 1 and G beta 2 and 40% homology with Saccharomyces cerevisiae G beta protein. Disruption of the gpb1 gene indicated that this gene is not required for vegetative cell growth. However, gpb1-disrupted haploid cells mated and sporulated faster than wild-type cells, both in sporulation (MEA) and in complex medium (YE): when examined 23 h after transfer to sporulation medium, 35% of gpb1-disrupted haploid pairs had undergone conjugation and sporulation, whereas only 3-5% of wild-type haploid pairs had done so. Overexpression of the gpb1 gene suppressed this facilitated conjugation and sporulation phenotype of gpb1-disrupted cells but did not cause any obvious effect in wild-type cells. Co-disruption of one of the two S. pombe G alpha-subunit genes, gpa2, in the gpb1-disrupted cells did not change the accelerated conjugation and sporulation phenotype of the gpb1- cells. However, co-disruption of the ras1 gene abolished the gpb1- phenotype. These results suggest that Gpb1 is a negative regulator of conjugation and sporulation that apparently works upstream of Ras1 function in S. pombe. The possible relationship of Gpb1 to two previously identified, putative G alpha proteins of S. pombe is discussed.
Mol Gen Genet 1996 Aug 27
PMID:The G protein beta subunit Gpb1 of Schizosaccharomyces pombe is a negative regulator of sexual development. 880

Mediators including the neuropeptide endothelin-1 (ET-1), which are released in response to injury, modulate the expression of cell adhesion molecules on leukocytes and endothelial cells. The mechanisms underlying this process are not clear. In this study we investigated the effect of endothelin-1 on the expression of tyrosine phosphorylated proteins in human blood monocytes. Endothelin-1 caused an increase in tyrosine phosphorylated proteins in monocytes in a time-dependent and dose-dependent manner, the Mr 60, 80 and 110 kDa proteins being the most prominent. This effect was blocked by pre-incubating the monocytes with the selective tyrosine kinase inhibitors genistein or herbimycin A. Endothelin-1 induced upregulation of tyrosine phosphorylated proteins appears to be mediated by the ETA receptor. Unlike our previously reported studies in endothelial cells, immunoprecipitation with anti-src or anti-JAK antibodies followed by immunoblotting with PY20 in human blood monocytes revealed that these proteins of Mr 60, 80 and 110 kDa were not related to src or JAK kinases. These findings suggest that ET- exerts its effect on monocytes by a pathway involving tyrosine kinases other than src or JAK kinases.
Mol Cell Biochem 1996 Jun 07
PMID:Endothelin-1 induces tyrosine phosphorylation in human blood monocytes. 881 7

Previous studies have demonstrated the presence of super-high affinity endothelin receptors with apparent Kd's on the order of pM in different brain tissues. This study was designed to characterize, in detail, the receptors present in SCP cells, a non-transformed sheep choroid plexus cell line. Competitive binding assays with receptor-selective ligands indicated the presence of at least three classes of binding sites: a conventional receptor of the ETA subtype with a Kd = 0.4 nM that mediates an increase in intracellular levels of inositol 1,4,5-trisphosphate (IP3)in response to ET-1 and two additional sites with much higher binding affinities. The latter two sites are not coupled to the common signal transduction pathways of IP3, cAMP and cGMP. Northern blot analysis confirmed the presence of only the ETA subtype mRNA in SCP cells. It remains to determined if the multiple binding sites are distinct gene products, multiple affinity states of a single receptor molecule or a result of cooperative association of one site with either the ligand or with other proteins.
Mol Cell Biochem 1996 Jun 07
PMID:Identification of conventional and novel endothelin receptors in sheep choroid plexus cells. 881 11

Endothelin-3 (ET-3) elicited a concentration-dependent positive inotropic effect on rabbit papillary muscle, the maximal response being approximately 65% of the maximal response to isoproterenol. ET-1 induced a positive inotropic effect over the concentration range below 10(-9) M, at which ET-3 did not produce a positive inotropic effect, but the maximal response to ET-1 was equivalent to or slightly lower than that of ET-3. The nonselective ET receptor antagonist PD 145065 effectively antagonized the positive inotropic effect of ET-3 in a concentration-dependent manner and abolished it at 10(-5) M. PD 145065 decreased the positive inotropic effect induced by ET1 at lower concentrations (< 10(-9) M) but it did not affect the main portion of the concentration-response curve for the positive inotropic effect, i.e., the effect induced by high concentrations (> 10(-9) M) of ET-1. PD 145065 antagonized also the positive inotropic effect of sarafotoxin S6c. PD 145065 inhibited the specific binding of [125I]ET-1 and of [125I]ET-3 with a high- and a low-affinity site for competition. ETB selective ligands, RES-701-1 and sarafotoxin S6c, displaced [125Iuc]ET-3 with high affinity but they scarcely affected the [125I]ET-1 binding. These findings indicate that different subtypes of the ET receptor are responsible for the induction of the positive inotropic effect of ET-3 and ET-1. ET receptors involved in the production of the positive inotropic effect in the rabbit ventricular myocardium have pharmacological characteristics that are different from those of conventional ET receptors originally classified based on the pharmacological findings in noncardiac tissues. The positive inotropic effect of ET-3 in the rabbit ventricular muscle may be mediated predominantly by ETA1 receptors that are susceptible to PD 145065 as well as BQ-123 and FR139317, and partially mediated by ETB receptors that are inhibitable with RES-701-1. ETA2 receptors that are resistant to ETA selective as well as nonselective antagonists may mainly be responsible for the positive inotropic effect of ET-1 in the rabbit ventricular muscle.
Mol Cell Biochem
PMID:Pharmacological characteristics of endothelin receptors in the rabbit ventricular myocardium: the nonselective endothelin receptor antagonist PD 145065 antagonizes the positive inotropic effect of endothelin-3 but not of endothelin-1. 890 57

The endothelin (ET) peptides have been identified in the CNS, but there is a paucity of information on their physiological roles. NG108-15 cells, a clonal strain of a neuroblastoma x glioma hybrid cell line, have been widely used in neurobiological research since they retain certain differentiated properties of the non-transformed parental cells. It is known that NG108-15 cells respond to the ET peptides, but only limited information is available on the characterization of the ET receptors that mediate these effects. The present study was designed to identify the type(s) of ET receptors on NG108-15 cells in a proliferative state by competitive binding assays using [125I]ET-1 as the radiolabelled ligand and the receptor-selective ligands. ET-1, ET-3, BQ-123, sarafatoxin-6-c and [Ala1,3,11,15]ET-1. The results suggested the presence of conventional ETA and ETB receptor subtypes, with ETA in excess over ETB. These findings were consistent with the results of Northern analysis in that mRNAs encoding the ETA and ETB receptor subtypes were identified in NG108-15 cells, with a preponderance of ETA to ETB. Of considerable interest was the observation of other ET-binding components with much higher affinities than the conventional receptors. It remains to be demonstrated if these particular binding components are functional and represent differ gene products or arise from association of the conventional ETA and ETB receptor subtypes with themselves or other structures, e.g. proteins or lipids, of CNS origin.
Cell Mol Biol (Noisy-le-grand) 1996 Dec
PMID:Endothelin binding to NG108-15 cells: evidence for conventional ETA and ETB receptor subtypes and super-high affinity binding components. 899 27

1. The receptor autoradiographic method done on the rat lower brain stem and cerebellum plus 125I-endothelin-1, BQ-123, an antagonist for the endothelin ETA receptor, and sarafotoxin S6c, an agonist for the ETB receptor, revealed minute amounts of the ETA receptor coexisting with the ETB receptor in the caudal solitary tract nucleus of the rat lower brain stem. 2. The ETB receptor is present predominantly in other parts of the lower brain stem. 3. Knowledge of the heterogeneous distribution of the central endothelin receptor subtypes aids in understanding the neurophysiology of endothelins.
Cell Mol Neurobiol 1997 Feb
PMID:The endothelin ETA receptor exists in the caudal solitary tract nucleus of the rat brain. 911 7

1. We used the quantitative receptor autoradiographic method plus 125I-endothelin-1 (125I-ET-1), BQ-123, a specific antagonist for the endothelin ETA receptor, and sarafotoxin S6c, a selective agonist for the ETB receptor to investigate the ET receptor in the rat pituitary gland. 2. The method revealed that the BQ-123-sensitive ETA receptor was present predominantly in the anterior lobe and Rathke's pouch. 3. The posterior lobe contained BQ-123-sensitive ETA and sarafotoxin S6c-sensitive ETB receptors, in almost the same proportion. There was no significant 125I-ET-1 binding to the intermediate lobe. 4. Knowledge of the heterogeneous distribution of ET receptor subtypes in the pituitary gland supplies information that will be pertinent to physiological investigations of the gland.
Cell Mol Neurobiol 1997 Feb
PMID:Endothelin receptors in rat pituitary gland. 911 11

Quantitative autoradiography employing the ETA selective ligand [125I]PD 151242 and the ETB selective ligand [125I]BQ3020 was used to assess the localization of ETA and ETB receptors in human uterus throughout the menstrual cycle. ETA and ETB receptors were present in endometrium and myometrium across the menstrual cycle. In myometrium, neither ETA nor ETB receptor density showed any detectable change across the menstrual cycle. ETA receptors were expressed in stroma throughout the endometrium and showed an increase in density in proliferative endometrium compared with secretory and menstrual endometrium. Endometrial ETB receptors were expressed at low density in the proliferative phase. In the early secretory phase there was an increase in ETB receptor density in the glandular epithelium of the basal region of the endometrium but not in functional endometrium. In the late secretory phase ETB receptor expression was increased in glandular epithelium throughout the endometrium. The highest density of ETB receptors was seen in menstrual endometrium, where they were present in stromal as well as epithelial cells. These results suggest that ovarian steroid hormones may play a role in the control of expression of ETA and ETB receptors in endometrial stromal and epithelial cells respectively.
Mol Hum Reprod 1996 Jun
PMID:Localization of endothelin receptors in human uterus throughout the menstrual cycle. 923 14

Endothelin-1 (ET-1), a peptide isolated from the culture medium of endothelial cells, mediates a variety of physiological and pathological responses including mitogenesis. We have compared the expression of ET receptors in untransformed versus ras-transformed NIH-3T3 murine fibroblasts and in untransformed versus SV40-transformed W138 (VA13) human fibroblasts by ligand binding and Northern analysis. NIH-3T3 and W138 cells displayed high affinity (200 and 220 pM) and high density (23,000 sites/cell and 14,000 sites/cell for NIH-3T3 and W138 cells, respectively) ET receptors. Competition binding experiments using subtype-selective ligands identified these receptors as the ETA subtype. Addition of ET-1 to the cells produced a concentration-dependent increase in intracellular calcium release. Both ras-transformed NIH-3T3 cells and SV40-transformed W138 cells (VA13) completely lacked [125I]ET-1 binding and failed to release calcium when exposed to ET-1. Northern analysis of the polyadenylated RNA (polyA RNA) isolated from untransformed and transformed cells revealed that the steady-state level of ETA receptor RNA was 90-95% less in transformed cells compared to untransformed cells. Thus, the loss of ET receptors as well as the receptor-mediated responses in transformed cells can be explained by down-regulation of ET receptor mRNA.
Mol Cell Biochem 1997 Oct
PMID:Absence of endothelin receptors and receptor mRNA in mammalian fibroblasts transformed with SV40 or ras oncogene. 935 30

There is increasing evidence that tumor expressed genes induce immune responses in cancer patients. To identify meningioma expressed antigens, we established a meningioma expression library which was screened with autologous serum. Out of 20 positive cDNA clones eight share high sequence homologies as determined by sequence analysis. These eight clones can be grouped into three classes which differ in length and which are characterized by specific sequence variations. The longest open reading frame was found to be 2412 bp encoding an immunoreactive antigen termed meningioma expressed antigen 6 (MEA6). Using five sequence specific primer pairs, somatic hybrid panel mapping revealed locations of the three classes on several human chromosomes including chromosomes 2, 3, 6, 7, 9, 13 and 14. The mapping results were confirmed by fluorescence in situ hybridization. RT-PCR showed consistent expression of all classes in several meningiomas and additional tissues using the same set of primer pairs as for chromosomal mapping. The expression data were confirmed by northern blot analysis. For the predicted amino acid sequence BLASTX revealed a homology to a human C219-reactive peptide which was previously isolated by an antibody directed against p-glycoprotein. Sequence properties of the MEA protein include an acidic activation domain, a proline-rich region and two coiled-coil domains indicating protein binding and activation functions.
Hum Mol Genet 1997 Nov
PMID:cDNA cloning and chromosomal mapping of a predicted coiled-coil proline-rich protein immunogenic in meningioma patients. 935 11


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