Effects of the tumour promoter okadaic acid on intracellular protein phosphorylation and metabolism.
Okadaic acid is a polyether derivative of 38-carbon fatty acid, and is implicated as the causative agent of diarrhetic shellfish poisoning. It is a potent tumour promoter that is not an activator of protein kinase C, but is a powerful inhibitor of protein phosphatases-1 and -2A (PP1 and PP2A) in vitro. 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. Our results indicate that PP1 and PP2A are the dominant protein phosphatases acting on a wide range of phosphoproteins in vivo. We also find that okadaic acid mimics the effect of insulin on glucose transport in adipocytes, which suggests that this process is stimulated by a serine/threonine phosphorylation event.
Haystead
T A
TA
Biochemistry Department, The University, Dundee, UK.
Sim
A T
AT
Carling
D
D
Honnor
R C
RC
Tsukitani
Y
Y
Cohen
P
P
Hardie
D G
DG
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D051381:Rats
D002273:Carcinogens; D004988:Ethers, Cyclic; D011506:Proteins; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D000103:Acetyl-CoA Carboxylase; D005947:Glucose