Disease relevance of PPP1R1A

• Evaluation of PAI-039 [{1-benzyl-5-[4-(trifluoromethoxy)phenyl]-1H-indol-3-yl}(oxo)acetic acid], a novel plasminogen activator inhibitor-1 inhibitor, in a canine model of coronary artery thrombosis [1].

High impact information on PPP1R1A

• Thus, phosphorylation of inhibitor-1 at threonine 75 represents a new mechanism of cardiac contractility regulation, partially through the alteration of sarcoplasmic reticulum calcium transport activity [2].
• Adenoviral-mediated expression of the constitutively phosphorylated threonine 75 inhibitor-1 in isolated myocytes was associated with specific stimulation of type-1 protein phosphatase activity and marked inhibition of the sarcoplasmic calcium pump affinity for calcium, resulting in depressed contractility [2].
• Inhibitor-1 represents a nodal integrator of two major second messenger pathways, adenosine 3',5'-cyclic monophosphate (cAMP) and calcium, which mediate its phosphorylation at threonine 35 and serine 67, respectively [2].
• Plasminogen activator inhibitor-1 activity decreased during rt-PA infusion and thereafter increased in all dogs, but less so in dogs given lys-plasminogen (p < 0.05 vs. those given saline solution before rt-PA) [3].
• We studied PP1 activity and protein and mRNA expression of the catalytic subunit of PP1 (PP1C) and protein levels of PP1-specific inhibitors [inhibitor 1 (Inh-1) and inhibitor 2 (Inh-2)] in the left ventricular (LV) myocardium of 6 dogs with heart failure (HF; LV ejection fraction, 23 +/- 2%) and 6 normal dogs [4].

Biological context of PPP1R1A

• The catalytic subunits derived from protein phosphatases-2Ao, 2A1 and 2A2 possessed identical substrate specificities, preferentially dephosphorylated the alpha-subunit of phosphorylase kinase, were unaffected by inhibitor-1 and inhibitor-2 and were inhibited by similar concentrations of ATP [5].
• The objective of this study was to test the hypothesis if thrombolysis induced by recombinant tissue-type plasminogen activator, (rt-PA) could be facilitated by inhibiting carboxypeptidase U (CPU, active Thrombin Activatable Fibrinolysis Inhibitor, TAFIa) activity [6].

Anatomical context of PPP1R1A

• Okadaic acid, a specific protein phosphatase inhibitor, induces maturation and MPF formation in Xenopus laevis oocytes [7].
• The sensitivity of red blood cells containing hemoglobins S and C to activation of K-Cl cotransport by osmotic swelling and acidification was reduced by okadaic acid, a specific protein phosphatase inhibitor [8].

Associations of PPP1R1A with chemical compounds

• The enzyme dephosphorylated and inactivated phosphorylase kinase and inhibitor 1, and dephosphorylated and activated glycogen synthase and acetyl-CoA carboxylase [9].
• OxyHb and blood CSF, in contrast, failed to produce consistent or marked changes in p21Ras precipitation. p21Ras inhibitors FTPase inhibitor 1 and manumycin abolished hemolysate-induced enhancement of p21Ras immunoprecipitation [10].
• MDCK cells cryopreserved in CryoStor CS 5 supplemented with an apoptotic inhibitor (Caspase I Inhibitor V), hereafter termed CryoStor CS 5N, resulted in a 24-h postthaw survival and recovery rate exceeding that of any other cryoprotective solution tested (85%) [11].
• Experiments were performed to examine whether the protein phosphatase inhibitor cantharidin inhibits the negative inotropic effect induced by endothelin-1 and carbachol in isolated canine ventricular trabeculae [12].

Other interactions of PPP1R1A

• Elucidation of the Effects of the CYP1A2 Deficiency Polymorphism in the Metabolism of 4-Cyclohexyl-1-ethyl-7-methylpyrido[2,3-d]pyrimidine-2-(1H)-one (YM-64227), a Phosphodiesterase Type 4 Inhibitor, and Its Metabolites in Dogs [13].

Analytical, diagnostic and therapeutic context of PPP1R1A

• Since the enzyme isolated from the glycogen complex by DEAE-cellulose chromatography could be inhibited by inhibitor-1 as well as the modulator protein, it was assumed that an unknown mechanism or factor present in the glycogen fraction was responsible for this reduced sensitivity of the protein phosphatase [14].
• In Vitro and In Vivo Metabolism of a Gamma-Secretase Inhibitor BMS-299897 and Generation of Active Metabolites in Milligram Quantities with a Microbial Bioreactor [15].

References