Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A peptide of unknown structure was found as a side product in a commercial preparation of the 1-34 fragment of bovine parathyroid hormone (PTH). CNBr cleavage and amino acid analysis showed that this peptide is the des-lys-13 form of 1-34 bovine PTH. The peptide thus represents a deletion mutant of PTH and structure-function studies are of interest. This peptide was a full agonist in the adenylyl cyclase bioassay for PTH, but its potency was about 5% of that found for the complete 1-34 peptide. Proton NMR studies showed that the pK values for the histidine residues in the des-lys-13 form were essentially identical to those of the intact peptide. However, pH-dependent changes in the chemical shifts for the tryptophan protons (residue 23) and several unidentified methyl group resonances were observed in the des-lys peptide. The latter are major shifts and probably represent ring-current effects; these were not seen in the intact 1-34 peptide. The results show that Lys-13 is important in the folding of the active domain of PTH, and are interpreted in the context of a previously published model for the folding of this hormone.
Mol Cell Endocrinol 1987 Jun
PMID:Deletion of lysine 13 alters the structure and function of parathyroid hormone. 310 80

The effects of 3.0 mM Mn2+ on parathyroid hormone (PTH) release, 45Ca fluxes and the cytoplasmic Ca2+ concentration (Ca2+i) were studied in vitro with use of parathyroid glands from rats and cattle. Mn2+ inhibited PTH release by about 70 and 60% at Ca2+ concentrations of less than 10 nM or 0.5 mM, respectively, and like the inhibitory effect of Ca2+, that of Mn2+ was rapid and reversible. Mn2+-induced inhibition of the PTH release was associated with reduction of 45Ca uptake by about 50% and a marked but temporary increase in 45Ca efflux. Mn2+ induced a rapid transient increase in Ca2+i provided that the intracellular release of Ca2+ had not already been triggered by previous exposure to 3.0 mM Ca2+. This initial action was apparently followed by influx of Mn2+, since pronounced quenching of the fluorescence from the Ca2+ indicator fura-2 was observed. The results indicate that Mn2+ behaves in several respects like a calcium analogue in parathyroid cells and may inhibit PTH release by interfering directly with the secretory machinery.
Mol Cell Endocrinol 1988 Sep
PMID:Calcium-agonistic action of Mn2+ in the parathyroid cell. 319 20

The promoter region of the human parathyroid hormone gene was fused to the Escherichia coli neo gene and introduced into GH4C1 rat pituitary and human HeLa cells. Both TATA boxes of the human parathyroid hormone gene accurately directed transcription in GH4C1 cells; the parathyroid hormone promoter was inactive in HeLa cells.
Mol Cell Biol 1986 May
PMID:Cell-specific expression of the human parathyroid hormone gene in rat pituitary cells. 378 80

The chromosomal localization of genes for parathyroid hormone (PTH), beta-globin cluster, c-Ha-ras-1, and insulin, all of which have previously been assigned to the short arm of chromosome 11, generated considerable interest because of their association with development of disease states. Furthermore, the availability of recombination data from family studies made the determination of their physical location on the chromosome necessary. Several investigators have attempted this; however, controversy has arisen concerning the location of beta-globin, insulin, and c-Ha-ras-1 genes. Thus, while the results of some investigators suggested that all three genes are situated in the 11p15 region, data of other investigators placed the beta-globin and insulin genes close to the centromere and c-Ha-ras-1 in a more proximal region than 11p15. The subchromosomal position of the PTH gene remains to be determined. We have performed in situ hybridization of meiotic pachytene bivalents with 3H-labeled cloned genomic probes of PTH, beta-globin, and insulin genes and find their germ-line positions to be the following: PTH at 11p11.21, beta-globin at 11p11.22, and insulin at 11p14.1. These data, when considered with our recent germ-line assignment of the c-Ha-ras-1 gene to 11p14.1, indicate the following relative order on 11p: cen-PTH-beta-globin-c-Ha-ras-insulin or cen-PTH-beta-globin-insulin-c-Ha-ras. The former order is consistent with genetic evidence from linkage analysis of DNA polymorphisms adjacent to these genes segregating in families.
Somat Cell Mol Genet 1985 Mar
PMID:Germ-line chromosomal localization of genes in chromosome 11p linkage: parathyroid hormone, beta-globin, c-Ha-ras-1, and insulin. 388 18

The effects of 17 beta-estradiol on proliferation and prolactin secretion by a clonal rat pituitary cell, GH3B6, have been investigated in a chemically defined medium (Ham's F12, transferrin, insulin and parathyroid hormone). Under these conditions, 17 beta-estradiol alone (5 X 10(-14)-5 X 10(-9) M) was not a mitogen for GH3B6 cells as shown by cell counts and DNA measurements. However, it slowed down the drop in prolactin production induced by culture in this chemically defined medium. After 3 and 7 days it stimulated PRL production up to 5 times in a dose-dependent manner. This secretory response was abolished by tamoxifen, and not mimicked by progesterone, testosterone or dexamethasone. The thyroliberin-induced stimulation of prolactin production occurred more rapidly (24 h) than and was additive to the 17 beta-estradiol response, suggesting that these two factors act through independent mechanisms. PRL neosynthesis in culture was attested to by the incorporation of [35S]methionine (5 h) into immunoprecipitable prolactin. Neither 17 beta-estradiol nor thyroliberin increases specifically prolactin radioactivity, although they strongly decreased the specific activity of prolactin in both cells and medium. This suggests that they mostly acted by decreasing PRL turnover rate.
Mol Cell Endocrinol 1985 Jan
PMID:17 beta-Estradiol regulates prolactin secretion but not cell proliferation of GH3B6 cells in chemically defined medium. 391 92

The sequence of bovine parathyroid hormone mRNA has been determined by sequence analysis of near full-length cloned DNA complementary to the mRNA. Restriction fragments hybridized to the mRNA and extended toward the 5' terminus with reverse transcriptase were analyzed to derive the sequence not present in cDNA. The reverse transcripts were heterogeneous in length with three major stopping points within 8 nucleotides of each other and a minor stop about 30 bases further toward the 5' terminus of the mRNA. The sequence of the gene corresponding to the minor reverse transcript begins with the sequence 5' XXXATATATAAAA which contains the consensus sequence for a TATA box, a putative eukaryotic promoter sequence. Assuming that the major reverse transcriptase stop nearest the 5' terminus of the mRNA, which is 24 bases downstream from the TATA box, represents the beginning of bovine PTH mRNA, the mRNA contains 672 nucleotides, 100 in the 5' noncoding region, 348 in the coding region and 224 in the 3' noncoding region. Bovine PTH mRNA contains 38% G and C bases. The 3' noncoding region is particularly rich in A and U bases with the last 100 nucleotides of the molecules containing 46% U and 32% A. As with other mRNAs, the sequences CG and UAG occur much less than expected. The 5' noncoding region does not contain an AUG before the initiator codon and contains two potential regions that could base-pair with sequences near the 3' terminus of 18S ribosomal RNA. The sequence AAUAAA is present 14 nucleotides from the polyadenylic acid at the 3' terminus. Bovine PTH mRNA exhibits extensive homology with human PTH mRNA.
Mol Cell Endocrinol
PMID:Nucleotide sequence of bovine parathyroid hormone messenger RNA. 618 74

Potassium-stimulated release of many hormones requires the presence of extracellular calcium. At variance with this mechanism, potassium-evoked parathyroid hormone (PTH) release from perifused dispersed bovine parathyroid cells also occurred in calcium-free medium containing 1 mM EGTA. Tetraethylammonium, which presumably suppresses the efflux of potassium from parathyroid cells, also stimulated PTH secretion. Removal of sodium did not suppress potassium-stimulated PTH secretion, but inhibited the release of the hormone evoked by calcium removal and by isoproterenol. Ouabain, on the other hand, suppressed the release of PTH evoked by calcium removal and by potassium, but not by isoproterenol. Unlike high potassium and removal of calcium, isoproterenol caused a parallel increase in cAMP release. In conclusion, PTH secretion is reversibly stimulated by potassium in the absence of extracellular calcium. Our findings suggest that potassium stimulates PTH secretion by a unique mechanism the nature of which remains to be elucidated.
Mol Cell Endocrinol 1983 Sep
PMID:Potassium stimulates parathyroid hormone release in the absence of extracellular calcium. 631 51

Several polypeptide hormones of apparently diverse structure and function have a number of similarities which suggest that there may be common features in their mechanism of action. These hormones are all composed of a single linear sequence of about 30 amino acids; their hydrophobic amino acids are regularly spaced at every third or fourth amino acid residue, allowing them to form amphipathic structures which can interact with phospholipids; a fragment at or near their N-terminus is required for biological activity. These hormones include glucagon, beta-endorphin, parathyroid hormone and calcitonin. A model is proposed in which all regions of the hormone bind to the receptor with comparable affinity except for a small segment which, when intact, triggers a conformational change in the receptor resulting in a further stabilization of the hormone-receptor complex. The activity of partial sequences and chemically modified forms of beta-endorphin, parathyroid hormone and glucagon are discussed in relation to this model.
Mol Cell Biochem 1983
PMID:Relationships among several different non-homologous polypeptide hormones. 631 22

Cytosolic factors in a 50--75% (NH4)2SO4 fraction of the 105 000 x g supernatant of the renal cortex modulated adenylate cyclase activity in membrane preparations enriched in renal tubular cell basal--lateral membranes. The crude factor preparation had no effect on basal activity but it contained components that augmented the stimulated of the enzyme by NaF, parathyroid hormone (PTH), prostaglandin E1 (PGE1), and inhibited the activation of the enzyme by GMP--PNP. The factor(s) potentiating the stimulation by the hormones was partially purified (13-fold) by DEAE-cellulose and Sephadex G-75 chromatography. During purification, the component(s) that increased hormone-stimulated adenylate cyclase was separated from those affecting the activity in the presence of NaF and GMP--PNP. The factor(s) enhanced the PTH- and PGE1-stimulated enzyme at all concentrations of hormone, suggesting that the affinity for the hormone was not affected. The factor(s) was heat-stable. Partial proteolysis with chymotrypsin greatly reduced the ability of the factor(s) to enhance hormonal responsive adenylate cyclase. However, the factor(s) was resistant to trypsin digestion. The effect of the factor was not due to GTP, nor was GTP necessary for its action. Ca2+ was not needed for the enhancing activity of the factor(s). These findings suggest the presence in the cytosol of the kidney cortex of a protein(s) that regulates the response of renal adenylate cyclase to hormones. The relationship between this kidney cytosolic factor and those reported in other tissues remains to be established.
Mol Cell Endocrinol 1981 Mar
PMID:Regulation of hormone(PTH and PGE1)-stimulated adenylate cyclase by renal cytosolic factors. 721 2

It has been previously reported that 8701-BC cells, derived from a primary carcinoma of the breast, constitutively express parathyroid hormone-related peptide (PTHrP) gene and that N-terminal PTHrP immunoreactivity can be found in cell medium. Here we have firstly measured immunoreactive PTHrP in 8701-BC cell medium using antibodies raised against midregion and C-terminal fragments, and also demonstrated the expression of PTH/PTHrP receptor by 8701-BC cells. Secondly, we have examined the role, if any, elicited by diverse PTHrP domains on 8701-BC cell proliferation, and invasive behaviour in vitro related to production of extracellular proteolytic enzymes. Our data show that PTHrP [1-34], and, to a minor extent, [67-86] and [107-139], are anti-mitogenic but 'invadogenic' for 8701-BC cells, and suggest that diverse enzymatic activities may contribute to cell invasion in response to different PTHrP fragments. In light of the present data on a chemoattractive role for PTHrP in vitro, we hypothesize that this protein might intervene in local control of the invasive process in breast carcinoma.
Mol Cell Endocrinol 1995 Jun
PMID:Parathyroid hormone-related peptide and 8701-BC breast cancer cell growth and invasion in vitro: evidence for growth-inhibiting and invasion-promoting effects. 755 86


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