Cyanobacterial nodularin is a potent inhibitor of type 1 and type 2A protein phosphatases.
The present study characterizes the inhibitory effects of nodularin, a recently isolated hepatotoxic compound from the cyanobacterium Nodularia spumigena, on type 1 (PP1), type 2A, (PP2A), type 2B (PP2B), and type 2C (PP2C) protein phosphatases. Both PP2A and PP1 were potently inhibited (IC50 = 0.026 and 1.8 nM, respectively) by nodularin, whereas PP2B was inhibited to a lesser extent (IC50 = 8.7 microM). Nodularin had no apparent effect on PP2C, alkaline phosphatase, acid phosphatase, insulin receptor tyrosine kinase, protein kinase A, phosphorylase kinase, or protein kinase C. In a whole-cell extract of T51B liver cells, nodularin inhibited PP1 and PP2A activity with a potency similar to that seen with their purified catalytic subunits. Thus, due to the high specificity of nodularin for PP2A and PP1, this hepatotoxin may prove to be useful as a probe for distinguishing the activity of these protein phosphatases in cell extracts.
Honkanen
R E
RE
Molecular Oncology Program, Cancer Research Center of Hawaii, University of Hawaii, Manoa, Honolulu 96813.
Dukelow
M
M
Zwiller
J
J
Moore
R E
RE
Khatra
B S
BS
Boynton
A L
AL
D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D000458:Cyanobacteria / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010762:Phosphorylase a / Q000378:metabolism; D010766:Phosphorylation; D011817:Rabbits
D001426:Bacterial Proteins; D006657:Histones; D010456:Peptides, Cyclic; C063998:nodularin; D010762:Phosphorylase a; D010749:Phosphoprotein Phosphatases