A potent synthetic peptide inhibitor of the cAMP-dependent protein kinase

H. C. Cheng, B. E. Kemp, R. B. Pearson, A. J. Smith, L. Misconi, S. M. Van Patten, D. A. Walsh

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As an important new reagent for studying the cAMP-dependent protein kinase, a 20-residue peptide has been synthesized that corresponds to the active site of the skeletal muscle inhibitor protein. This synthetic peptide inhibits the protein kinase competitively with a K(i) = 2.3 nM; its sequence, Thr-Thr-Tyr-Ala-Asp-Phe-Ile-Ala-Ser-Gly-Arg-Thr-Gly-Arg-Arg-Asn-Ala-Ile- His-Asp, is that of a peptide previously reported by us which was derived from the native inhibitor protein by V8 protease digestion. Studies with analogues of this peptide show that its high affinity binding to the protein kinase (as also of the inhibitor protein) appears to be due to it mimicking the protein substrate by binding to the catalytic site via the arginine-cluster basic subsite [(11)Arg-Arg(15)], and also to a critical contribution from one or more of the 6 N-terminal residues [[(1)Thr-Phe(6)]. The availability of this high affinity synthetic peptide should open up a variety of avenues to probe the cellular actions of cAMP.

Original languageEnglish
Pages (from-to)989-992
Number of pages4
JournalJournal of Biological Chemistry
Issue number3
Publication statusPublished - 9 Jul 1986
Externally publishedYes

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