Disease relevance of Ppp1r1a

• Conversely, inhibiting phosphatase activity with the protein phosphatase inhibitor tautomycin, or increasing extracellular calcium concentration, results in the 10-Hz tetanus, inducing LTP [1].
• Protein phosphatase inhibitor-1 mRNA expression correlates with neoplastic transformation of epithelial liver cells and progression of hepatocellular carcinomas [2].
• Okadaic acid (OA), a protein phosphatase inhibitor, was found to induce hyperphosphorylation and reorganization of vimentin intermediate filaments in 9L rat brain tumor cells [3].
• Microcystin LR (MCLR) is a naturally occurring protein phosphatase inhibitor and potent hepatotoxin produced by strains of Microcystis aeruginosa [4].

Psychiatry related information on Ppp1r1a

• Okadaic acid (OA), a protein phosphatase inhibitor, is used as a research model of Alzheimer's disease to induce tau phosphorylation and neuronal death [5].

High impact information on Ppp1r1a

• We report here that okadaic acid rapidly stimulates protein phosphorylation in intact cells, and behaves like a specific protein phosphatase inhibitor in a variety of metabolic processes [6].
• The loading of CA1 cells with microcystin LR, a membrane-impermeable protein phosphatase inhibitor, or calmodulin antagonists also blocked or attenuated LTD [7].
• Coinjection of oocytes with striatal mRNA and antisense oligodeoxynucleotides directed against the protein phosphatase inhibitor DARPP-32 dramatically reduced the PKA enhancement of NMDA responses [8].
• Furthermore, a protein phosphatase inhibitor and the intracellularly applied CaM-KII markedly enhanced GABA-mediated currents in Purkinje neurons [9].
• We now show that a phosphopeptide of 31 amino acids, corresponding to residues 8-38 of the protein phosphatase inhibitor DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of Mr 32,000), mimics the inhibitory action of dopamine on Na+,K(+)-ATPase activity in renal tubule cells from the ascending limb of the loop of Henle [10].

Biological context of Ppp1r1a

• A cDNA encoding the complete amino acid sequence of rat protein phosphatase inhibitor-1 was obtained by screening a skeletal muscle library [11].
• Detection and quantification of protein phosphatase inhibitor-1 gene expression in total rat liver and isolated hepatocytes [12].
• The mRNA expression of protein phosphatase inhibitor-1 (inhibitor-1) in rat liver was demonstrated using highly sensitive semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) [12].
• In isolated rat hepatocytes, the protein phosphatase inhibitor okadaic acid exerts a strong inhibitory effect on autophagy, which can be partially overcome by certain protein kinase inhibitors like the isoflavone genistein [13].
• The protein phosphatase inhibitor okadaic acid (> 100 nM) caused an abrupt and complete cessation of primary rat hepatocyte cell cycle progression at the restriction point in late G1 [14].

Anatomical context of Ppp1r1a

• Two cAMP-regulated inhibitors of protein phosphatase-1, inhibitor-1 (I1) and a dopamine- and cAMP-regulated phosphoprotein, M(r) = 32,000 (DARPP-32), are enriched in the choroid plexus [15].
• Our results also raise the possibility that inhibition of phosphatase-1, as a result of I1 and DARPP-32 phosphorylation, might be part of a final common pathway in the action of several factors that are known or thought to alter cerebrospinal fluid production [15].
• In synaptosomes, the only treatment found to increase Ser8 phosphorylation was okadaic acid (a protein phosphatase inhibitor), which increased 32P incorporation into all four phosphorylation sites [16].
• Hormonal regulation of protein dephosphorylation. Identification and hormonal regulation of protein phosphatase inhibitor-1 in rat adipose tissue [17].
• Microcystin-LR, a protein phosphatase inhibitor structurally distinct from okadaic acid, also antagonized the trimeric G-protein-mediated inhibition of secretory vesicle formation but, in contrast to okadaic acid, alone was sufficient to stimulate this process [18].

Associations of Ppp1r1a with chemical compounds

• Cortisol resplacement therapy restores protein phosphatase inhibitor activity, decreases increased protein phosphatase activity, and restores normal epinephrine-induced activation of phosphorylase b kinase and phosphorylase and epinephrine inhibition of phosphorylase phosphatase [19].
• Doxorubicin-induced changes appeared similar to the degeneration observed after treatment with a protein kinase activator (phorbol 12-myristate 13-acetate) or a serine-threonine protein phosphatase inhibitor (okadaic acid) [20].
• Several drugs and hormones that are known to alter fluid secretion and that increase cAMP levels (forskolin, isoproterenol, vasoactive intestinal peptide) or cGMP levels (atrial natriuretic peptide) or that may use additional second messenger pathways (5-HT), increase the phosphorylation of I1 and DARPP-32 in rat choroid plexus [15].
• Similar to G(i) inhibition, a protein phosphatase inhibitor, calyculin A (3 x 10(-8) M), selectively enhanced the beta(2)-AR but not beta(1)-AR-mediated contractile response [21].
• Protein phosphatase activities have been measured under conditions designed to minimize the influence of effectors of these enzymes, and a thermostable protein phosphatase inhibitor, termed inhibitor-2, has been used as a probe to specifically inhibit type 1 protein phosphatase [22].

Enzymatic interactions of Ppp1r1a

• The protein phosphatase inhibitor pervanadate robustly increased the amount of tyrosine-phosphorylated mGluR5, suggesting the receptor is subject to an endogenous, active cycle of phosphorylation and dephosphorylation [23].

Regulatory relationships of Ppp1r1a

• Stress-induced dephosphorylation could be mimicked by alkaline phosphatase and suppressed by the protein phosphatase inhibitor okadaic acid (OA), indicating that PP2A in oligodendrocytes is activated by stress [24].
• 3. The monoamine and glutamate agonists both induced Fos-like protein exclusively in striatal neurons that constitutively expressed the protein phosphatase inhibitor DARPP-32 (dopamine and cAMP-regulated phosphoprotein) [25].
• 4. In all cases described above, the increases in activity of acetyl-CoA carboxylase were blocked by treatment with the cell-permeable protein phosphatase inhibitor, okadaic acid [26].
• Protein phosphatase inhibitor cantharidin inhibits steroidogenesis and steroidogenic acute regulatory protein expression in cultured rat preovulatory follicles [27].

Other interactions of Ppp1r1a

• The effect of Act D on ET-1- and PDGF-BB-induced ERK-2 activation was mimicked by the protein phosphatase inhibitor sodium orthovanadate [28].
• The protein phosphatase inhibitor okadaic acid was just as potent as vasopressin and glucagon in causing desensitization [29].
• In addition, the protein phosphatase inhibitor pervanadate (vanadyl hydroperoxide) was found to increase tyrosine phosphorylation of NR2D subunit threefold in brain slices, implying an active cycle of phosphorylation and dephosphorylation in situ [30].
• Phosphatase holoenzyme inhibitor (PHI)-1 is one of the newest members of the family of protein phosphatase inhibitor proteins [31].
• Regulation of the transmodulated epidermal growth factor receptor by cholera toxin and the protein phosphatase inhibitor okadaic acid [32].

Analytical, diagnostic and therapeutic context of Ppp1r1a

• Molecular cloning of protein phosphatase inhibitor-1 and its expression in rat and rabbit tissues [11].
• The extent of phosphorylation of protein phosphatase inhibitor-1 in skeletal muscle rose about 2.5-fold during 60 min of perfusion of the rat hemicorpus preparation and then did not change over the following 30 min [33].
• With immunoblotting we examined the abundance of DARPP-32 and the functionally similar but more widespread inhibitor of PP-1, inhibitor-1 (I-1) [34].
• The localization and ontogenic changes in the gene expression for phosphatase inhibitor-1 (I-1) were analyzed by in situ hybridization histochemistry, and they were compared with those for three catalytic subunits of protein phosphatase type 1 (PP-1) [35].
• In addition, double labeling immunocytochemistry indicated that Fos-like protein was expressed preferentially in striatal neurons containing the protein phosphatase inhibitor, DARPP-32 [36].

References