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

摘要

>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.