Accession Number : ADA302987
Title : Lipid-Dependent Membrane Enzymes. Kinetic Modelling of the Activation of Protein Kinase C by Phosphatidylserine.
Descriptive Note : Rept. for 1 Feb 87-31 Jan 91,
Corporate Author : VANDERBILT UNIV NASHVILLE TN
Personal Author(s) : Sandermann, Heinrich, Jr. ; Duncan, Thomas M.
PDF Url : ADA302987
Report Date : JAN 1991
Pagination or Media Count : 7
Abstract : A previously developed kinetic theory for Upid-dependent membrane enzymes (Sandermann, H. (1982) Fur. J. Biochem. 127, 123-128)15 used to examine the activation of protein kinase C by phosphatidylserine. Hill-coefficients ranging up to 11 have been reported for activation in mixed micelles with Triton X-1OO. On the basis of this uniquely high degree of cooperativity, protein kinase C has been postulated to represent a new class of lipid-dependent membrane enzymes (Newton, k and Koshland, D.E., Jr. (1989) J. Biol. Chem. 264, 14909-14915). In contrast, activation in the absence of Triton X-100 has led to Hill-coefficients of only % 2.6. In order to resolve the apparent discrepancy, activation is DOW considered to involve binding of PS monomers to interacting sites on the enzyme, a non-activating PS trapping process also occurring in the presence of Triton X-100. Estimates for trapping are made for several sets of published data for micellar activation. The kinetic model developed here successfully fits each data set using a Hill-coefficient of only 3.0. An influence of Ca2 +/ ions or of a two-step mechanism of lipid-protein interaction are considered as possible molecular explanations. It is concluded (i) that lipid activation of protein kinase C may proceed without unique cooperativity and (ii) that ligand trapping could provide another means for 'threshold-type' kinetic regulation of membrane enzyme nnd receptor systems.
Descriptors : *MEMBRANES(BIOLOGY), *ENZYMES, *LIPIDS, *KINETIC THEORY, DATA BASES, IONS, ACTIVATION, INTERACTIONS, DEFORMATION, SITES, MONOMERS, KINETICS, COLLOIDS, SENSE ORGANS, PHOSPHATASES, FUR.
Subject Categories : Biochemistry
Distribution Statement : APPROVED FOR PUBLIC RELEASE