Disease relevance of PTP

• Examples of a new class of phytase related to protein tyrosine phosphatases (PTP) were recently isolated from several anaerobic bacteria from the rumen of cattle [1].
• One isolate, Selenomonas lacticifex, contained two distinct PTP-like phytase sequences, suggesting that multiple phytate hydrolyzing enzymes are present in this bacterium [1].
• Their activation contributes to PSP inhibition by adenosine during hypoxia [2].

High impact information on PTP

• Using a full-length cloned bovine PTP cDNA and synthetic oligonucleotides corresponding to human PTP cDNA, which is identical to human islet cell regeneration factor, we analyzed the expression of PTP in pancreas and brain [3].
• In situ hybridization localized expression to pyramidal neurons in the cerebral cortex, the same population that contains neurofibrillary tangles and high levels of immunoreactive PTP [3].
• The relationship of phosphorylation to the potential physiologic importance of PSP remains to be determined [4].
• The primary protein phosphorylated had a Mr of 68,000 and coeluted with newly synthesized parathyroid secretory protein (PSP) on Bio-Gel chromatography and on polyacrylamide gel electrophoresis [4].
• Immunoblotting identified the association of PSP with parathyroid cell membranes in a Ca2+-dependent manner [5].

Biological context of PTP

• Plasma desorption mass spectrometry and amino acid sequence analysis now confirm that bovine PTP contains two disulfide-bonded polypeptides, an A chain of 101 amino acid residues with a molecular weight of 11,073 and a B chain of 35 residues with a molecular weight of 3970 [6].
• Phosphorylation sites on tyrosine-phosphorylated casein, a model PTP substrate, were characterized [7].
• The synthesis of the amino acid sequence found in bovine prothrombin precursor 13-29 (PTP 13-29) has been achieved by solid-phase synthesis of the bis(acetamidomethyl)-protected linear peptide followed by cyclization to the monomeric disulfide [8].
• Our results suggest that the inactivation of the LMr PTP by anionic and cationic surfactants involved both electrostatic and hydrophobic interactions, and that the interactions enzyme-surfactants probably occurred at or near the active site [9].
• We have now extended these studies to determine the effects of the vitamin D3 metabolite on parathyroid secretory protein (PSP) gene expression [10].

Anatomical context of PTP

• Comparison of bovine PTP with other proteins reveals significant structural relatedness with the single-chain homologues from human and rat pancreas and with the motif associated with Ca2(+)-dependent carbohydrate recognition domains [6].
• A novel observation is that Ser4Ala blocks the formation of PTP bacterial inclusion bodies [11].
• However, it is notable that production of catestatin itself (CgA(344)(-)(364)) utilizes more unusual cleavage sites at the NH(2)-terminal sides of downward arrow R and downward arrow RR basic residue sites, consistent with the cleavage specificities of the chromaffin granule cysteine protease "PTP" that participates in proenkephalin processing [12].
• Storage of isolated mitochondria at -80 degrees C prior to the isolation of the PTP decreases the maximal activity of the unidirectional transport of phosphate (Pi) in reconstituted vesicles [13].
• The phosphate transport protein (PTP) has been isolated from beef heart mitochondria in the presence of cardiolipin and reconstituted in asolectin and phosphatidylcholine vesicles [13].

Associations of PTP with chemical compounds

• Based upon the bovine PTP cDNA structure, the two chains of the protein result from cleavage of a single polypeptide with removal of a dipeptide between the NH2-terminal A chain and COOH-terminal B chain [6].
• Thus, the function relevant transmembrane helix A, with Cys 28 about equidistant from the two inner membrane surfaces, is in close contact with parts of transmembrane helix A of the other subunit in the functional homodimeric PTP [14].
• Two peptides based on casein phosphorylation sites and one peptide based on the tyrosine phosphorylation site of reduced, carboxamidomethylated and maleylated (RCM) lysozyme were tested as PTP substrates [7].
• 3. The protein tyrosine phosphatase (PTP) inhibitors Na3VO4 (200 microM) and dephostatin (20 microM) potentiated ICl,swell activated by mild hypotonicity by 47 +/- 9 and 69 +/- 15%, respectively [15].
• The inhibition of the PTP by adriamycin is reversed by KCl and prevented by MgSO4 [13].

Analytical, diagnostic and therapeutic context of PTP

• In this study, the diversity of PTP-like phytase gene sequences in the rumen was surveyed by using the polymerase chain reaction (PCR) [1].
• Isoelectric focusing of double-labeled samples ([35S]methionine and 32Pi) revealed comigration of the two radioactive markers at a pH of 4.6, which was similar to that of purified PSP [4].
• Sequence analysis suggests that the bovine pancreatic thread protein encoding gene is, in fact, the bovine homologue of the HIP gene [16].
• A radioimmunoassay for PSP was developed to identify the protein in tissue extracts and in incubation medium [17].
• Proliferation of IND cells [( 3H]thymidine uptake) was suppressed only if REG cells were treated with anti-Lyt-2 and C before co-culture [18].

References