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The level of protein phosphorylation is dependent on the relative activities of both protein kinases and protein phosphatases. By comparison with protein kinases, however, there have been considerably fewer studies on the functions of serine/threonine protein phosphatases. This is partly due to a lack of specific protein phosphatase inhibitors that can be used as probes. In the present study we characterize the inhibitory effects of microcystin-LR, a hepatotoxic cyclic peptide associated with most strains of the blue-green algae Microcystis aeruginosa found in the Northern hemisphere, that proves to be a potent inhibitor of type 1 (IC50 = 1.7 nM) and type 2A (IC50 = 0.04 nM) protein phosphatases. Microcystin-LR inhibited the activity of both type 1 and type 2A phosphatases greater than 10-fold more potently than okadaic acid under the same conditions. Type 2A protein phosphatases in dilute mammalian cell extracts were found to be completely inhibited by 0.5 nM microcystin-LR while type 1 protein phosphatases were only slightly affected at this concentration. Thus, microcystin-LR may prove to be a useful probe for the study and identification cellular processes which are mediated by protein phosphatases.
R E Honkanen, and
J Zwiller, and
R E Moore, and
S L Daily, and
B S Khatra, and
M Dukelow, and
A L Boynton
May 1990,
FEBS letters,
R E Honkanen, and
J Zwiller, and
R E Moore, and
S L Daily, and
B S Khatra, and
M Dukelow, and
A L Boynton
January 1993,
Biochemical and biophysical research communications,
R E Honkanen, and
J Zwiller, and
R E Moore, and
S L Daily, and
B S Khatra, and
M Dukelow, and
A L Boynton
September 2003,
Bioorganic & medicinal chemistry letters,
R E Honkanen, and
J Zwiller, and
R E Moore, and
S L Daily, and
B S Khatra, and
M Dukelow, and
A L Boynton
November 1995,
Biochemical and biophysical research communications,
R E Honkanen, and
J Zwiller, and
R E Moore, and
S L Daily, and
B S Khatra, and
M Dukelow, and
A L Boynton
October 1987,
Molecular endocrinology (Baltimore, Md.),
R E Honkanen, and
J Zwiller, and
R E Moore, and
S L Daily, and
B S Khatra, and
M Dukelow, and
A L Boynton
December 1990,
FEBS letters,
R E Honkanen, and
J Zwiller, and
R E Moore, and
S L Daily, and
B S Khatra, and
M Dukelow, and
A L Boynton
January 1992,
Preparative biochemistry,
R E Honkanen, and
J Zwiller, and
R E Moore, and
S L Daily, and
B S Khatra, and
M Dukelow, and
A L Boynton
October 1997,
The Journal of antibiotics,
R E Honkanen, and
J Zwiller, and
R E Moore, and
S L Daily, and
B S Khatra, and
M Dukelow, and
A L Boynton
December 1994,
Cancer research,
R E Honkanen, and
J Zwiller, and
R E Moore, and
S L Daily, and
B S Khatra, and
M Dukelow, and
A L Boynton
September 1993,
The Journal of biological chemistry,
