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
Okadaic acid, a ptotein phosphatase inhibitor, induces sister-chromatid exchanges depending on the presence of bromodeoxyuridine
TL;DR: Results suggest a common involvement of topo I for SCE formation by OA, BA and CPT and in addition to SCE induction, OA resulted in an increase of mitotic cells which were characterized by a marked chromosome condensation.
Journal ArticleDOI
Cytotoxicity of yessotoxin and okadaic acid in mouse T lymphocyte cell line EL-4.
Alicia Martín-López,J. J. Gallardo-Rodríguez,A. Sánchez-Mirón,Francisco García-Camacho,Emilio Molina-Grima +4 more
TL;DR: The cytotoxic effects of YTX and OA reported here, and the previously demonstrated potential of these toxins to regulate the activity of EL-4 cells through the regulation of TCR expression, rise reasonable concern about possible risks for human health associated to the chronic exposure to low amounts of Y TX or OA itself or enhanced by the presence of other shellfish toxins specially by a population potentially at risk such as immunocompromised patients.
Journal ArticleDOI
Activation of PKCδ and p38δ MAPK during okadaic acid dependent keratinocyte apoptosis
TL;DR: The data indicate that OA is an agent that regulates both keratinocyte differentiation and apoptosis, and that this regulation is mediated via activation of a PKCδ/p38δ signaling cascade.
Journal ArticleDOI
Belizeanic Acid: A Potent Protein Phosphatase 1 Inhibitor Belonging to the Okadaic Acid Class, with an Unusual Skeleton
TL;DR: The isolation ofBelizeanic acid, a novel metabolite belonging to the okadaic acid class of protein phosphatase inhibitors, supports the biogenetic pathway previously reported for this class of compounds.
Journal ArticleDOI
Preliminary characterization of the role of protein serine/ threonine phosphatases in the regulation of human lung mast cell function
TL;DR: The data suggest that okadaic acid regulates responses in HLMC by interacting with PPs, but it has not been possible to determine whether either PP1 or PP2A or both PPs are involved in the okADAic acid‐induced inhibition of mediator release from HLMC.
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.