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)

It previously has been shown that digestion of bovine parathormone (bPTH) with cathepsin-D results in rapid cleavage of the hormone between Phe34 and Val35 yielding PTH(1-34) and PTH(35-84). Since bPTH also contains a Phe at residue 7 we have conducted additional studies to determine whether cleavage at this position could occur. We have found that following longer incubation periods of hormone and enzyme, 2 additional peptides are generated; PTH(8-34) and PTH(1-7). Time course studies demonstrated that these 2 fragments are formed from the (1-34) peptide generated through the initial cleavage at Phe34-Val35 of PTH. The identification of the bPTH(8-34) was accomplished through amino acid analysis and N-terminal sequencing. bPTH(8-34) behaved as a PTH antagonist in an in vitro mouse calvarial bone resorption assay. Although bPTH(8-34) did not affect the PTH-stimulated cAMP response when added simultaneously with PTH, preincubation of bone cells with this peptide caused desensitization of the PTH-stimulated cAMP response.
Mol Cell Endocrinol 1986 Feb
PMID:Formation of parathormone 8-34 by cathepsin-D digestion of parathormone and its efficacy as a hormone antagonist. 300 87

In the present studies we used the calcium (Ca2+)-sensitive dye Quin-2 to determine whether the cytosolic (Cyt) Ca2+ mediates the effects of extracellular (EC) Ca2+ on cAMP accumulation through changes in adenylate cyclase and phosphodiesterase activity in bovine parathyroid cells (bPTC). In dispersed (d) bPTC, increasing the EC Ca2+ from 0.5 to 2 mM produces a rise in the Cyt Ca2+ from 179 to 646 nM which is associated with a 52% inhibition of agonist-stimulated cAMP accumulation. Over this range of free Ca2+ adenylate cyclase activity decreased by approx. half (57%) and phosphodiesterase activity increases 2-fold (101%) suggesting that changes in the Cyt Ca2+ can account for the effects of EC Ca2+ on cAMP through changes in these enzymes. Unlike dbPTC, 4-day-old cultured bPTC show only a 23% suppression of cAMP by high EC Ca2+ and a reduced rise in the Cyt Ca2+ from 0.5 to 3 mM EC Ca2+. Although there is no reduction in the Ca2+ sensitivity of adenylate cyclase, phosphodiesterase activity shows no change at varied free Ca2+. Thus, this diminished Ca2+ sensitivity of phosphodiesterase activity, and the decreased rise in Cyt Ca2+ relative to EC Ca2+ may both contribute to the resistance to the effects of EC Ca2+ on cAMP content in cultured cells. Because in addition to Cyt Ca2+, protein kinase C may also mediate the effects of EC Ca2+ on PTH release, we studied the effects of TPA (12-alpha-tetradecanoylphorbol 13-acetate) on agonist-stimulated cAMP in dbPTC.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1986 May
PMID:Role of cytosolic calcium in the control of cAMP content by calcium in bovine parathyroid cells. 301 57

PTH is initially synthesized as a larger precursor, containing a 25 amino acid signal sequence. Modification of cDNA encoding the hormone precursor resulted in the synthesis of proteins whose signal sequences were shortened at their amino termini. The effects of these mutations were analyzed using a cell-free translation system and rat pituitary GH4 cells in culture. Removal of the first six amino acids of the signal sequence had no effect on the efficiency or kinetics of protein processing as measured in the two assay systems. Mutants lacking 10 or 13 amino acids were not processed efficiently in the cells, nor were they translocated across microsomes in the cell-free translation system. These studies suggest that a modest change in the hydrophobic domain of the signal sequence, which might not have been predicted to alter function, led to a dramatic decline in signal activity.
Mol Endocrinol 1987 Sep
PMID:Consequences of amino-terminal deletions of preproparathyroid hormone signal sequence. 315 80

A novel PTH-like peptide has recently been purified and cloned from human tumors associated with the syndrome of humoral hypercalcemia of malignancy. We surveyed the expression of mRNAs encoding this peptide in normal tissues by Northern analysis. One or more low abundance hybridizing transcripts was identified in poly(A)+ RNA prepared from human keratinocytes, thyroid, bone marrow, and fibroblasts, from bovine hypothalamus, pituitary, parathyroid, adrenal cortex, and adrenal medulla, and from rat brain, stomach mucosa, and fetal but not adult liver. One or more hybridizing transcripts was also identified in poly(A)+ RNA prepared from a number of established lines, including rat pituitary (GH4), rat pheochromocytoma (PC 12), human osteosarcoma (TE-85), and human medullary carcinoma (TT) cells. Northern analysis of mRNAs from abnormal human parathyroid tissue revealed an overexpression of transcripts for the PTH-like peptide which appeared to be specific for adenomatous or autonomous glands. These findings suggest that the PTH-like peptide is expressed in a number of endocrine and nonendocrine tissues, that it is developmentally expressed in at least one tissue (fetal liver), and that the regulation of its expression is abnormal in human parathyroid adenomas.
Mol Endocrinol 1988 Dec
PMID:Expression of messenger ribonucleic acids encoding a parathyroid hormone-like peptide in normal human and animal tissues with abnormal expression in human parathyroid adenomas. 321 62

cDNA encoding human preproPTH (hpreproPTH) was expressed in Escherichia coli to study the processing of the precursor to hPTH and its secretion by the bacterial secretory apparatus. We first constructed hybrid genes that differed randomly in the distance between the E. coli lac promoter's ribosomal binding site and DNA encoding a fusion protein with beta-galactosidase activity and the prepro sequence of hpreproPTH on the aminoterminus. Starting with clones identified as efficient producers of beta-galactosidase on indicator agar plates, the coding sequence for hpreproPTH was reconstituted intact. In a different construction we placed the hpreproPTH coding sequence downstream from the lac promoter at a distance of 12 base pairs from the ribosomal binding site. PTH immunoreactive proteins from multiple clones were identified by protein gel electrophoresis and by protein microsequencing. PTH-related proteins encoded by different plasmids were shown to be hpreproPTH with amino-terminal extensions of either two or four amino acids and as authentic hpreproPTH. Two hPTH fragments, hPTH(3-84) and hPTH(8-84), were also observed. The trypsin accessibility of hpreproPTH and of the two hPTH fragments in pulse-chase, cell-fractionation experiments using intact and lysed spheroplasts lets us conclude that the mammalian signal sequence directs hpreproPTH to the surface of the spheroplast membrane but is not appropriately cleaved by the signal peptidase.
Mol Endocrinol 1987 Jan
PMID:Human preproparathyroid hormone synthesized in Escherichia coli is transported to the surface of the bacterial inner membrane but not processed to the mature hormone. 333 11

Proliferating cells derived from hominoid species contain electrophoretically separable forms of triosephosphate isomerase (TPI), including a constitutive isozyme and major and minor cell proliferation specific isozymes. Genetic studies have shown that the constitutive and inducible isozymes are products of the same structural gene. A procedure has been developed for the rapid isolation of the constitutive and major proliferation specific TPI isozymes from human lymphoblastoid B cells. [35S]methionine labeled isozymes were purified through several steps of polyacrylamide gel electrophoresis in sufficient quantities for turnover studies and preliminary structural analysis. The intact isozymes were subjected to 23 steps of automated Edman degradation; both preparations yield a [35S] PTH-methionine only at cycle 14, as expected if the protein is TPI. Neither isozyme contains a blocked NH2-terminus and length heterogeneity at the amino terminal does not exist. A comparison of the two purified isozymes on 2-D PAGE confirms that the constitutive isozyme consists of only type 1 subunits while the major proliferation specific isozyme is composed of a type 1 subunit and a unique type 2 subunit. The type 1 and type 2 subunits differ by at least four charge units under native, nondenaturing conditions of electrophoresis but do not differ in molecular mass. The difference between the type 1 and type 2 subunits is covalent, as the difference in isoelectric point between the two subunits is stable to both 2% SDS and 8 M urea. The expression of TPI-2 does not correlate with the existence of the labile asparagine residues. Turnover studies indicate that the level of each subunit is regulated by differences in rates of synthesis rather than degradation but a precursor-product relationship between the subunits was not observed. Thus the mechanism for synthesis of TPI-2 must operate either during mRNA processing or nascent peptide synthesis and then only in cells from hominoid species.
Mol Cell Biochem 1986 Jun
PMID:Hominoid triosephosphate isomerase: characterization of the major cell proliferation specific isozyme. 348 12

The relationship of the paraphyseal-choroid plexus complex to parathyroid gland function was investigated in adult frogs. Light microscopy and morphometric analysis indicated that total parathyroid gland volume, cell volume and vascular volume doubled by 7-28 days after surgical removal of the paraphyseal-choroid plexus complex (paraphysectomy). This increase correlated with the appearance of large Golgi-associated vesicles, an increase in the apparent number of cytoplasmic dense-core granules, and PTH within the parenchymal cells as monitored by immunofluorescence. Twelve months after paraphysectomy, parathyroid glands became cystic with a central fluid-filled cavity surrounded by a stratified cuboidal cell layer. The parenchymal cells of cystic glands contained numerous cytoplasmic dense-core granules and were also positive for PTH. Radioimmunoassay of cystic parathyroid fluid indicated a PTH concentration of 2 micrograms/microliter; however, analysis by SDS-PAGE indicated a wide range of proteins in cystic fluid. The results of this study indicate that paraphysectomy induces stimulation of the parathyroid glands and suggest a role for the paraphyseal-choroid plexus complex in the regulation of amphibian parathyroid gland function.
Mol Cell Endocrinol 1986 Sep
PMID:Paraphysectomy-induced stimulation of parathyroid glands in mature frogs (Rana catesbeiana): evidence for telencephalic regulation of parathyroid gland function. 352 13

A combined morphometric and ultrastructural study was performed on so called emperipolesis or internal wandering of myeloid cells in the cytoplasm of large mature megakaryocytes. Measurements were made on material from a total of 115 patients comprising a normal control group and 5 groups with subtypes of chronic myeloproliferative diseases, including primary (essential, idiopathic) thrombocythemia (PTH). A significant increase in this peculiar phenomenon was noted in myeloproliferative disorders and especially in PTH where the frequency of emperipolesis showed a positive correlation with the number of anuclear cytoplasmic fragments sectioned, with the circular deviation of the shapes of megakaryocytes and with the extent to which the peripheral thrombocyte count was elevated. Electron microscopy in selected cases displayed the integrity of the plasma membranes of engulfed hematopoietic cells within the dilated cavities of the megakaryocytic demarcation membrane system (DMS) and no evidence of phagocytosis. Moreover there was a close relationship between engulfed myeloid cells and the presumptive sites of platelet shedding which had their openings from the cisternal lumina of the DMS. Our results demonstrate that emperipolesis of hematopoietic cells within megakaryocytes should not be regarded as a special nosological feature, but as an indication of enforced thrombocytogenetic activity which is expressed particularly in PTH.
Virchows Arch B Cell Pathol Incl Mol Pathol 1984
PMID:Emperipolesis--a peculiar feature of megakaryocytes as evaluated in chronic myeloproliferative diseases by morphometry and ultrastructure. 614 4

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

We examined the effects of varying the extracellular magnesium (Mg2+) concentration at different extracellular calcium (Ca2+) concentrations on cytosolic Ca2+ and PTH release in dispersed bovine parathyroid cells using the fluorescent, Ca2+-sensitive dye QUIN-2. Raising extracellular Mg2+ from 0.5 to 5 mM produced significant (p less than 0.01) increases in cytosolic Ca2+ from 228 +/- 13 to 306 +/- 15 nM at 0.5 mM extracellular Ca2+ and from 199 +/- 9 to 299 +/- 19 nM at 1.0 mM extracellular Ca2+. The concentration of extracellular Mg2+ which produced half of the maximal increase in cytosolic Ca2+ was significantly higher, however, at 0.5 mM than at 1.0 mM extracellular Ca2+ [3.3 +/- 0.16 (n = 5) vs. 2.0 +/- 0.08 mM Mg2+ (n = 6), p less than 0.01]. High extracellular Mg2+ (5 mM) was associated with a similar inhibition of PTH release at 0.5 and 1.0 mM Ca2+ [67 +/- 2% (n = 4) and 59 +/- 5% (n = 7), respectively], but half-maximal inhibition of secretion occurred at a higher Mg2+ concentration with 0.5 than with 1.0 mM Ca2+ [3.5 +/- 0.43 (n = 4) vs. 2.0 +/- 0.21 mM (n = 5), respectively, p less than 0.01]. In contrast, in cells exposed to subphysiological extracellular Ca2+ concentrations (less than or equal to 10(-6) M), 5 mM Mg2+ had little or no effect on either cytosolic Ca2+ or PTH release. At 10 mM extracellular Mg2+ with less than or equal to 10(-6) M Ca2+, PTH release was inhibited 55 +/- 3% (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1984 Dec
PMID:Interaction of extracellular calcium and magnesium in the regulation of cytosolic calcium and PTH release in dispersed bovine parathyroid cells. 651 May 51


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