Disease relevance of PPA1

• Primary BAC1 and PPA1 resembled enteric adenocarcinomas immunophenotypically; on the other hand, BAC2 demonstrated a pattern of protein expression similar to that of Type II pneumocytes [1].
• Cases were classified as Type I (mucinous) bronchioloalveolar carcinoma (BAC1); Type II (nonmucinous) bronchioloalveolar carcinoma (BAC2); conventional PPA with BAC1-like areas (PPA1); or conventional PPA with BAC2-like foci (PPA2) [1].
• The activation of leukocytes induced by HP-NAP is completely inhibited by pertussis toxin, wortmannin, and PP1 [2].
• By comparison, affinity isolation of cellular GADD34/PP1 complexes showed that PP1 bound near the C terminus of GADD34 (amino acids 483 to 619), a region that shows sequence homology with the virulence factors ICP34.5 of herpes simplex virus and NL-S of avian sarcoma virus [3].
• Inorganic pyrophosphatase (PPiase) activity was measured in cell fractions of rat, mouse, and human erythrocytes; normal rat liver; Novikoff hepatoma; Morris 3924A hepatoma; and mouse Ehrlich and Sarcoma 37 ascites tumors [4].

Psychiatry related information on PPA1

• Both affected members of PPA1 with autopsies had frontotemporal lobar degeneration with tau-negative ubiquinated inclusions [5].
• Progranulin Mutations in Primary Progressive Aphasia: The PPA1 and PPA3 Families [5].
• In this study, we analyzed high expression of protein phosphatase (PP) 2A in Alzheimer's disease brain compared to that of the control brain, which result from hyperphosphorylation of histone H1 [6].

High impact information on PPA1

• The inactive cytosolic form of PP-1 (PP-1I) can be activated in vitro through the glycogen synthase kinase-3-catalyzed phosphorylation of its inhibitory subunit (inhibitor-2), but the physiological significance is unclear.(ABSTRACT TRUNCATED AT 400 WORDS)[7]
• The activities of PP-1 and PP-2B are controlled by the second messengers cyclic AMP and calcium [7].
• Yotiao, an NMDA receptor-associated protein, bound the type I protein phosphatase (PP1) and the adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA) holoenzyme [8].
• Hence, yotiao is a scaffold protein that physically attaches PP1 and PKA to NMDA receptors to regulate channel activity [8].
• The main regulatory step takes place at the level of ADP-glucose synthesis, a reaction catalyzed by ADP-Glc pyrophosphorylase (PPase) [9].

Chemical compound and disease context of PPA1

• Furthermore, the V804M/E805K tandem lesion confers resistance to the small molecule receptor tyrosine kinase inhibitor, PP1, suggesting a mode of action distinct from that known for classical MEN 2B mutations [10].
• A eukaryotic type serine/threonine kinase and phosphatase in Streptococcus agalactiae reversibly phosphorylate an inorganic pyrophosphatase and affect growth, cell segregation, and virulence [11].
• We report in this study that, when nontransformed CV1 epithelial cells and Hs578T breast cancer cells are treated with the chemotherapeutic agent cytosine arabinoside (Ara-C), Thr-821 of Rb is rapidly dephosphorylated concomitant with dissociation of the PP1 regulatory subunit PNUTS (phosphatase nuclear targeting subunit) from PP1 enzyme [12].
• Our results show that inhibition of PP1 activity with microcystin-LR (50 nmol/l) or okadaic acid (100 nmol/l) increased phenylephrine- and KCl-induced contraction to a greater extent in aortic rings from rats exposed to hypoxia (10% O(2)) for 48 h than in rings from normoxic animals [13].
• The inorganic pyrophosphatase activity of a soluble extract from the strict anaerobe, sulfate-reducing, Desulfovibrio vulgaris, is readily resolved into two peaks [14].

Biological context of PPA1

• A de novo case of trisomy 10p: gene dosage studies of hexokinase, inorganic pyrophosphatase and adenosine kinase [15].
• Assignment of the inorganic pyrophosphatase gene locus (PP) to chromosome 10 in man [16].
• A full-length cDNA, PPA2 (Prunus persica H+-ATPase 2) and three partial cDNAs (PPA1, PPA3 and PPA4) for the plasma-membrane H+-ATPase from peach trees were isolated by reverse transcription (RT)-coupled rapid amplification of cDNA ends (RACE) polymerase chain reaction (PCR) [17].
• Here, we show that PPA1- and deoxy-PPJ1 display potent anti-inflammatory and apoptosis inducing activities similar to PGA1 and deoxy-PGJ2 [18].
• PP-1 can be inhibited by cyclic AMP in a variety of cells through the A-kinase-catalyzed phosphorylation of inhibitor-1 and its isoforms [7].

Anatomical context of PPA1

• Inorganic pyrophosphatase was present mainly in the soluble fraction and in the mitochondria [19].
• A new rapid assay for inorganic pyrophosphatase has been developed and the procedure optimised for measurement of the enzyme in human neutrophils [20].
• Purification and kinetic properties of human erythrocyte Mg2+-dependent inorganic pyrophosphatase [21].
• Based on these data, we propose that dephosphorylation of U2 and U5 snRNP components by PP1/PP2A family phosphatases facilitates essential structural rearrangements in the spliceosome during the transition from the first to the second step [22].
• Lower fasting PP-1 activity in cytosol and glycogen fractions plus lower insulin-stimulated PP-1 activity could explain, in part, reduced insulin-stimulated glycogen synthase in skeletal muscle of insulin-resistant subjects [23].

Associations of PPA1 with chemical compounds

• Inorganic pyrophosphatase (pyrophosphate phosphohydrolase, EC 3.6.1.1) from human erythrocyte hemolysates has been purified up to 10 000-fold [21].
• We determined total PP-1 activity in muscle biopsies from insulin-sensitive and -resistant nondiabetic Pima Indians [24].
• Tautomycin, an inhibitor of PP1, inhibited blue light-induced H(+) pumping, phosphorylation of the plasma membrane H(+)-ATPase in guard cell protoplasts, and stomatal opening [25].
• The growth arrest and DNA damage-inducible protein, GADD34, was identified by its interaction with human inhibitor 1 (I-1), a protein kinase A (PKA)-activated inhibitor of type 1 protein serine/threonine phosphatase (PP1), in a yeast two-hybrid screen of a human brain cDNA library [3].
• The phospho-CREB (P-CREB) phosphatase activity present in nuclear extracts coelutes with protein Ser/Thr phosphatase type 2A (PP2A) on Mono Q, amino-hexyl Sepharose, and heparin agarose columns and was chromatographically resolved from nuclear protein Ser/Thr-phosphatase type 1 (PP1) [26].

Regulatory relationships of PPA1

• Unexpectedly, Alk PPase inhibited aromatase activity in a dose-dependent manner in the presence, as well as in the absence, of ATP/Mg/Ca [27].

Other interactions of PPA1

• Therefore we conclude that HA synthesis during chondrocyte differentiation is regulated at the level of the substrate-provider gene, UDPG-PPase, as well as the HAS genes [28].
• Aminomethylenebisphosphonate (AMBP; HC(PO3)2NH2) is a potent, specific inhibitor of the PPase of higher plant vacuoles (V-PPase) [29].
• In the present study, we report the identification of one of the clones as UDP-glucose pyrophosphorylase (UDPG-PPase) and propose a possible function for this enzyme in regulating hyaluronan (HA) synthesis in hypertrophic cartilage [28].
• Eleven distinctly changed proteins were detected, in which four proteins (serine/threonine kinase 4, glutathione S-transferase p1-1, glycoprotein IX and soluble inorganic pyrophosphatase) were reported to be relative to MAPK pathways, while the other seven proteins may be new elements of substrates of the kinases [30].
• Inorganic pyrophosphatase, PPi:glucose phosphotransferase, and carbamyl-P:glucose phosphotransferase activities of glucose 6-phosphatase were totally latent [31].

Analytical, diagnostic and therapeutic context of PPA1

• Immunoprecipitation of PP1 from cell extracts resulted in a 10.4 +/- 3.8-fold enrichment of PKA activity [32].
• This was evidenced by filtration experiments as well as by the accessibility of synthesized pyrophosphate to soluble inorganic pyrophosphatase [33].
• Computer-assisted sequence alignment further revealed that lambda-PPase residues Asp20, His22, Asp49, His76, Arg53, and Arg73 lie within three larger regions of PPase sequence identity with the consensus sequence (DXH-(approximately 25)-GDXXD-(approximately 25)-GNHD/E) [34].
• Cell fractionation and PP1 catalytic subunit isolation studies support the notion that the pRb-directed phosphatase activity involves subpopulations of PP1 catalytic subunits [35].
• Using RT-PCR and sequence analyses we showed that DARPP-32, PP-1, and D1-R genes were not restricted to cultured luteinized GCs, but were expressed in vivo, in the corpus luteum (CL) of the rhesus monkey throughout its entire life span [36].

References