Differential effects of fatty acid and phospholipid activators on the catalytic activities of a structurally novel protein kinase from rat liver.

The lipid responsiveness of the structurally unique protein kinase, referred to as PAK-1, recently isolated from rat liver [(1994) J. Biol. Chem. 269, in press], is characterised by the high sensitivity (low micromolar) of its ribosomal S6(229-239) peptide kinase activity to both cardiolipin and the cis-unsaturated fatty acids and insensitivity to phosphatidylserine. Autophosphorylation of PAK-1 exhibited even greater sensitivity (submicromolar) to cardiolipin, but was relatively less affected by phosphatidylserine. Oleate, the most potent activator of PAK-1's peptide kinase activity was relatively ineffectual with autophosphorylation. These and other unusual characteristics, including high levels of basal catalytic activities, suggest a novel mechanism of regulation distinct from that of the protein kinase Cs.