Evidence for negative control in protein kinase C substrate specificity

The peptide Leu-Asp-Asp-Ser-Lys-Arg-Val-Ala-Lys-Arg-Lys-Leu-Ile-Glu, which corresponds to sequence 124 to 137 of c-erb-A protein, was synthesized and tested as substrate for protein kinase C (PKC). Although a typical recognition sequence for PKC, consisting of a cluster of basic residues, is found o...

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Bibliographic Details
Published inInternational journal of peptide and protein research Vol. 33; no. 4; p. 304
Main Authors Ricouart, A, Tartar, A, Sergheraert, C
Format Journal Article
LanguageEnglish
Published Denmark 01.04.1989
Subjects
Amino Acid Sequence
Animals
Brain - enzymology
Feedback
Kinetics
Molecular Sequence Data
Oligopeptides - chemical synthesis
Phosphorylation
Protein Kinase C - metabolism
Rats
Substrate Specificity
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Summary:The peptide Leu-Asp-Asp-Ser-Lys-Arg-Val-Ala-Lys-Arg-Lys-Leu-Ile-Glu, which corresponds to sequence 124 to 137 of c-erb-A protein, was synthesized and tested as substrate for protein kinase C (PKC). Although a typical recognition sequence for PKC, consisting of a cluster of basic residues, is found on the C-terminus side of serine, its phosphorylation was totally prevented by the presence of the two acidic residues on the amino-terminus side. Three analogs in which aspartyl residues were successively replaced with alanine were studied and the influence of the acidic side chain in modulating phosphorylation by PKC was thus possible to determine. The results show that the presence of a single aspartyl residue located in positions i-1 or i-2 with respect to the phosphorylable residue can almost totally abolish the positive effect of a highly favorable cluster of basic residues. These observations highlight the role of negative substrate specificity determinants in settling the protein substrate profile of protein kinase C.
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1989.tb01286.x