We propose that the principle driving force allowing protein kinase C (PKC)
to insert partway into membranes is the transient creation of an interior
hydrophilic phase within the membrane. We further suggest that this phase i
s composed of non-bilayer-forming elements, such as diacylglycerol or phorb
ol eaters. We used the combination of fluorescence resonance energy transfe
r (using fluorescently labeled phospholipid molecules and the endogenous tr
yptophan residues of PMC) and fluorescence quenching by the water-soluble r
eagent potassium iodide. The experimental system used micelles and purified
PKC. Our model accounts for both the established kinetic data on PKC as we
ll as the physical requirements of protein-membrane interaction. Moreover,
it establishes PHC as the first example of a partially embedded membrane pr
otein, and provides a mechanism to account for its activation. (C) 2001 Aca
demic Press.