Abstract
CAMP-dependent protein kinase is activated through the dissociation of active catalytic subunits from a regulatory dimer. The regulatory subunit consists of 4 cAMP-binding sites and 2 binding sites for catalytic subunits. Under well defined experimental conditions, protein kinase activation obeys apparent positive cooperativity and is linearly coupled to cAMP binding. The simulation of theoretical models is used for testing working hypotheses. The proposed stoichiometry of protein kinase activation may account for the experimentally observed properties of the system. The restrictive conditions under which theory and experimental observations are compatible are: functional dependence between the 2 monomers of the regulatory dimer, the only complexes which can accumulate at equilibrium in the considered conditions are R2C2, (cAMP)2R2C and (cAMP)4R2 (where R and C are the regulatory and catalytic subunits of protein kinase). An experimental procedure is proposed in order to check the validity of the theoretical predictions. The determination of the sequence of events leading to activaiton or inactivation of protein kinase is discussed.

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