5′‐AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP‐activated protein kinase. Studies using bacterially expressed human protein phosphatase‐2Cα and native bovine protein phosphatase‐2Ac

Abstract

Human protein phosphatase‐2Cα (PP2Cα) was purified to homogeneity after expression in Escherichia coli. AMP inhibited the dephosphorylation of AMP‐activated protein kinase (AMPK), but not phosphocasein, by PP2Cα. The concentration dependence and the effects of other nucleotides (ATP and formycin A‐5′‐monophosphate) suggest that AMP acts by binding to the same site which causes direct allosteric activation of AMPK. A similar, although less pronounced, effect was observed with another protein phosphatase (PP2A_c). We have now shown that AMPK activates the AMPK cascade by four mechanisms, which should make the system exquisitely sensitive to changes in AMP concentration.