Protein kinase C pseudosubstrate prototope: structure-function relationships.

C House; B E Kemp

doi:10.1016/0898-6568(90)90022-3

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Protein kinase C pseudosubstrate prototope: structure-function relationships.

C House·B E Kemp

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Abstract

A structure-function study of the protein kinase C (PK-C) pseudosubstrate sequence (R19FARK-GALRQKNV31) has been undertaken. The role of specific residues was investigated using an alanine substitution scan. Arg-22 was the most important determinant in the inhibitor sequence, since substitution of this residue by alanine gave a 600-fold increase in the IC50 value to 81 +/- 9 microM. Substitutions of other basic residue also increased the IC50, 5-, 11- and 24-fold for the Ala-19, Ala-23 and Ala-27 substitutions, respectively. The importance of basic residues in determining the potency of the pseudosubstrate peptide reflects the requirements for these residues in peptide substrate phosphorylation. The residues Gly-24, Leu-26 and Gln-28 were also important for pseudosubstrate inhibitor potency. The large difference in the IC50 value for the [A22]PK-C(19-31) peptide makes it a valuable control in studies employing the pseudosubstrate peptide to explore functional roles of PK-C.

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Amino Acid Sequence Animals Kinetics Molecular Sequence Data Peptides Phosphorylation Protein Kinase C Rats Structure-Activity Relationship Substrate Specificity Journal Article Research Support, Non-U.S. Gov't

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C House, B E Kemp. 1990. Protein kinase C pseudosubstrate prototope: structure-function relationships.. https://doi.org/10.1016/0898-6568(90)90022-3

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