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

Abstract

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 V _max 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.