Synthetic myelin basic protein peptide analogs are specific inhibitors of phospholipid/calcium-dependent protein kinase (protein kinase C)

Abstract

Synthetic peptide analogs of the bovine myelin basic protein (MBP) corresponding to residues 104–118 were found to specifically inhibit phospholipid Ca 2+ -dependent protein kinase (protein kinase C). The peptides [Ala 107]MBP(104–118) and [Ala 113]MBP(104–118) inhibited protein phosphorylation of intact MBP, histone H1 and peptide phosphorylation with MBP(104–123), MBP(104–118) or [Ala 105]MBP(104–118) as substrates. The inhibitor peptides [Ala 107]MBP(104–118) and [Ala 113]MBP(104–118), containing alanine in place of the arginine recognition sites, apparently inhibited the enzyme noncompetitively with respect to substrates, with IC 50 values ranging from 46–145 and 28–62 μM, respectively. These peptide analogs did not inhibit cyclic AMP-dependent protein kinase or myosin light chain kinase but inhibited phospholipid Ca 2+ -dependent phosphorylation of endogenous proteins in the total, solubilized fraction of rat brain.