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
Cytoskeletal disruption is the key factor that triggers apoptosis in okadaic acid-treated neuroblastoma cells
TL;DR: Results demonstrate that collapse of mitochondrial membrane potential is accessory in the execution of apoptosis, which is directly dependent on cytoskeletal changes.
Journal ArticleDOI
Okadaic acid-sensitive protein phosphatases constrain phrenic long-term facilitation after sustained hypoxia.
Julia E. R. Wilkerson,Irawan Satriotomo,Tracy L. Baker-Herman,Jyoti J. Watters,Gordon S. Mitchell +4 more
TL;DR: In this paper, the authors showed that spinal protein phosphatase inhibition would relieve this braking action of protein-phosphatases, thereby revealing pLTF after SH, but not sustained hypoxia (SH).
Journal ArticleDOI
A myofibrillar protein phosphatase from rabbit skeletal muscle contains the β isoform of protein phosphatase‐1 complexed to a regulatory subunit which greatly enhances the dephosphorylation of myosin
TL;DR: The properties of PP1M and the previously characterised glycogen-associated form of protein phosphatase-1 (PP1G), indicate that the subcellular localisation and substrate specificity ofPP1 is determined by its interaction with specific targetting subunits.
Journal ArticleDOI
Silibinin suppresses the maintenance of colorectal cancer stem-like cells by inhibiting PP2A/AKT/mTOR pathways.
TL;DR: Silibinin, which inhibits colon CSLCs self‐renewal and sphere formation by suppressing the PP2Ac/AKT Ser473/mTOR pathway, may be a compound for developing new strategies in modulating CSLC's in cancer therapy.
Journal ArticleDOI
Meiotic activation of rat pachytene spermatocytes with okadaic acid: the behaviour of synaptonemal complex components SYN1/SCP1 and COR1/SCP3
TL;DR: Data support the hypothesis that phosphorylation of SYN1/ SCP1 and COR1/SCP3 targets their removal from the chromosomes and that activity of the kinases involved correlates with the presence of these two proteins on the chromosomes.
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.