Inhibitory effect of a marine-sponge toxin, okadaic acid, on protein phosphatases. Specificity and kinetics
Corinna Bialojan,Akira Takai +1 more
Reads0
Chats0
TLDR
Kinetic studies showed that okadaic acid acts as a non-competitive or mixed inhibitor on the okadaIC acid-sensitive enzymes.Abstract:
The inhibitory effect of a marine-sponge toxin, okadaic acid, was examined on type 1, type 2A, type 2B and type 2C protein phosphatases as well as on a polycation-modulated (PCM) phosphatase. Of the protein phosphatases examined, the catalytic subunit of type 2A phosphatase from rabbit skeletal muscle was most potently inhibited. For the phosphorylated myosin light-chain (PMLC) phosphatase activity of the enzyme, the concentration of okadaic acid required to obtain 50% inhibition (ID50) was about 1 nM. The PMLC phosphatase activities of type 1 and PCM phosphatase were also strongly inhibited (ID50 0.1-0.5 microM). The PMCL phosphatase activity of type 2B phosphatase (calcineurin) was inhibited to a lesser extent (ID50 4-5 microM). Similar results were obtained for the phosphorylase a phosphatase activity of type 1 and PCM phosphatases and for the p-nitrophenyl phosphate phosphatase activity of calcineurin. The following phosphatases were not affected by up to 10 microM-okadaic acid: type 2C phosphatase, phosphotyrosyl phosphatase, inositol 1,4,5-trisphosphate phosphatase, acid phosphatases and alkaline phosphatases. Thus okadaic acid had a relatively high specificity for type 2A, type 1 and PCM phosphatases. Kinetic studies showed that okadaic acid acts as a non-competitive or mixed inhibitor on the okadaic acid-sensitive enzymes.read more
Citations
More filters
Journal ArticleDOI
Investigation of the distribution and excretion of okadaic acid in mice using immunostaining method.
TL;DR: This paper describes the distribution and excretion of okadaic acid administered orally to mice and examined by immunostaining method, finding that a considerable amount of OA was accumulated in the liver, but no symptoms, such as bleeding, were observed.
Journal ArticleDOI
Inhibitors of protein phosphatase-1 and -2A; two of the major serine/threonine protein phosphatases involved in cellular regulation
TL;DR: The broad specificity type-1 and type-2A protein phosphatases (PPs) have emerged as important enzymes in the regulation of eukaryotic cell function as mentioned in this paper.
Journal ArticleDOI
A significant increase in both basal and maximal calcineurin activity in the rat pilocarpine model of status epilepticus.
Jonathan E. Kurz,Dan Sheets,J. Travis Parsons,Aniruddha Rana,Robert J. DeLorenzo,Severn B. Churn +5 more
TL;DR: The data demonstrate that status epilepticus resulted in a significant increase in both basal and maximal calcineurin activity, and was found to be NMDA‐receptor activation dependent.
Journal ArticleDOI
Apoptosis induced by protein phosphatase 2A (PP2A) inhibition in T leukemia cells is negatively regulated by PP2A-associated p38 mitogen-activated protein kinase.
TL;DR: PP2A inhibition triggered the intrinsic pathway of apoptosis, which was enhanced by a mitochondrial feedback amplification loop, and pharmacologic inhibition of p38 MAPK exacerbated OA-induced DNA fragmentation and loss of delta psi(m) in T leukemia cells, suggesting that, in this instance, the p38MAPK signaling pathway promoted cell survival.
Journal ArticleDOI
Activation of calcium-dependent potassium channels in rat brain neurons by neurotrophin-3 and nerve growth factor
TL;DR: Results indicate that NT-3 stimulates BK channel activity in cortical neurons through a signaling pathway that involves Trk tyrosine kinase, phospholipase C, and protein dephosphorylation and is calcium-dependent.
References
More filters
Journal Article
Protein Measurement with the Folin Phenol Reagent
TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.
Journal ArticleDOI
The direct linear plot. A new graphical procedure for estimating enzyme kinetic parameters
TL;DR: A new plot is described for analysing the results of kinetic experiments in which the Michaelis-Menten equation is obeyed, and provides clear and accurate information about the quality of the observations, and identifies aberrant observations.
Journal ArticleDOI
The kinetics of enzyme-catalyzed reactions with two or more substrates or products. II. Inhibition: nomenclature and theory.
TL;DR: A nomenclature is proposed to describe different types of inhibitions of enzyme-catalyzed reactions, particularly for reactions with more than one substrate and product, and the rate equations for such inhibitions are discussed.
Journal ArticleDOI
Discovery of A Ca2+-and calmodulin-dependent protein phosphatase
TL;DR: The serine residue on the a-sub unit, as well as that on the@subunit, becomes phosphorylated in vivo in response to adrenaline, suggesting that it may have a physiological function.
Journal ArticleDOI
The protein phosphatases involved in cellular regulation. 1. Classification and substrate specificities.
TL;DR: Examination of the amino acid sequences around each phosphorylation site does not support the idea that protein phosphatase specificity is determined by the primary structure in the immediate vicinity of the phosphorylated site, and demonstrates that proteinosphatase-1 and protein phosph atase 2A have very broad substrate specificities.