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.
Kerr
D E
DE
Oncogen, Seattle, Washington 98121.
Kissinger
L F
LF
Gentry
L E
LE
Purchio
A F
AF
Shoyab
M
M
D002460:Cell Line; D002472:Cell Transformation, Viral; D004075:Diglycerides / Q000378:metabolism* / Q000494:pharmacology; D004789:Enzyme Activation; D005989:Glycerides / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007700:Kinetics; D010449:Peptide Mapping; D010748:Phosphopeptides / Q000032:analysis; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D013329:Structure-Activity Relationship
D004075:Diglycerides; D005989:Glycerides; D010748:Phosphopeptides; D011493:Protein Kinase C