Isozyme-specific inhibition of protein kinase C by RNA aptamers.
In vitro selection technology has been used to purify RNA aptamers from a random sequence pool that can bind to, and specifically inhibit, protein kinase C beta II. Two of the selected RNA aptamers bind to this isozyme of protein kinase C with nanomolar affinities and inhibit activation with unprecedented selectivity; the highly related, alternatively spliced beta I isozyme, which differs by 23 residues, is inhibited with 1 order of magnitude lower potency; the next most similar isozyme, alpha, shows no detectable inhibition. The production of isozyme-specific inhibitors of protein kinase C opens the possibilities for dissecting the roles of specific protein kinase Cs in the myriad of intracellular signalling pathways.
Conrad
R
R
Department of Chemistry, Indiana University, Bloomington 47405.
Keranen
L M
LM
Ellington
A D
AD
Newton
A C
AC
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D017931:DNA Primers; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D012326:RNA Splicing
D017931:DNA Primers; D007527:Isoenzymes; D012313:RNA; D011493:Protein Kinase C