Nucleic Acids Research, Vol 27, Issue 2 439-445, Copyright © 1999 by Oxford University Press
B Dong and RH Silverman
RNase L is the 2',5'-oligoadenylate (2-5A)-dependent endoribonuclease that
functions in interferon action and apoptosis. One of the intriguing, albeit
unexplained, features of RNase L is its significant homology to protein
kinases. Despite the homology, however, no protein kinase activity was
detected during activation and RNA cleavage reactions with human RNase L.
Similarly, the kinase plus ribonuclease domains of RNase L produced no
detectable protein kinase activity in contrast to the phosphorylation
obtained with homologous domains of the related kinase and
endoribonuclease, yeast IRE1p. In addition, neither ATP nor pA(2'p5'A)3was
hydrolyzed by RNase L. To further investigate the function of the kinase
homology in RNase L, the conserved lysine at residue 392 in protein
kinase-like domain II was replaced with an arginine residue. The resulting
mutant, RNase LK392R, showed >100-fold decreases in 2-5A-dependent
ribonuclease activity without reducing 2-5A- or RNA-binding activities. The
greatly reduced activity of RNase LK392Rwas correlated to a defect in the
ability of RNase L to dimerize. These results demonstrate a critical role
for lysine 392 in the activation and dimerization of RNase L, thus
suggesting that these two activities are intimately linked.
ARTICLES
Alternative function of a protein kinase homology domain in 2', 5'- oligoadenylate dependent RNase L
Department of Cancer Biology, NN10, The Lerner Research Institute, The Cleveland Clinic Foundation,9500 Euclid Avenue, Cleveland, OH 44195, USA.
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