Negative interactions between phosphorylation of acetyl-CoA carboxylase by the cyclic AMP-dependent and AMP-activated protein kinases

We have reported previously that cyclic AMP-dependent protein kinase phosphorylates two sites on acetyl-CoA carboxylase (site 1: Arg-Met-Ser(P)-Phe, and site 2: Ser-Ser(P)-Met-Ser-Gly-Leu), while the AMP-activated protein kinase also phosphorylates site 1, plus site 3 (Ser-Ser-Met-Ser(P)-Gly-Leu), the latter being two residues C-terminal to site 2. We now report that prior phosphorylation of site 2 by cyclic AMP-dependent protein kinase prevents the subsequent phosphorylation of site 3 and the consequent large decrease in Vmax produced by the AMP-activated protein kinase. Similarly, prior phosphorylation of site 3 by the AMP-activated protein kinase prevents subsequent phosphorylation of site 2 by cyclic AMP-dependent protein kinase.