The double-stranded RNA-dependent protein kinase (PKR) is believed to
mediate cellular antiviral responses, function as a tumor suppressor,
and regulate cell growth and differentiation. Its activation is depend
ent on double-stranded RNA (dsRNA) structures but these interactions a
re not fully understood. The possibility of direct interaction between
dsRNA and the arginine and lysine-rich region of PKR (residues 54-74)
was examined using synthetic peptides. We found that addition of a sy
nthetic peptide corresponding to residues 54-74 of murine PKR or resid
ues 60-80 of human PKR inhibited the autophosphorylation and activatio
n of the kinase by either poly(l)-poly(C) or the 82-nucleotide-long TA
R RNA. Gel-shift analysis indicated that the peptides disrupted the ki
nase-TAR complex by binding directly to TAR RNA. These findings deline
ate at least one dsRNA-binding domain in PKR which may be important fo
r its cellular activation. (C) 1996 Academic Press, Inc.