Structural requirements of diacylglycerols for binding and activating phospholipid-dependent, Ca++-sensitive protein kinase.

Phospholipid-dependent, Ca++-sensitive protein kinase (protein kinase C) is activated by phorbol esters and diacylglycerols. A series of diacylglycerols was synthesized with different substituents at positions 1 and 2 in order to expand known structure-activity relationships for these compounds with respect to binding and activating purified protein kinase C. Compounds were synthesized with saturated and unsaturated long chain fatty acyl groups at position 1 and acetyl, butyryl, or hexanoyl groups at position 2. Binding to protein kinase C correlated well with in-vitro activation of the enzyme. These diacylglycerols activated protein kinase C in an intact cellular system causing the phosphorylation of pp60c-src. This indicates that the length of the fatty acyl group at C2 is critical and that the existence of unsaturation in the fatty acyl group at C1 is not essential.