Regulatory subunit myristoylation antagonizes calcineurin phosphatase activation in yeast

Abstract

The Ca2+/calmodulin-stimulated protein phosphatase calcineurin is a critical component of Ca2+ signaling cascades in eukaryotic cells. Myristoylation of the regulatory subunit of calcineurin (CNB) is conserved from yeast to humans. Here, we show that CNB myristoylation antagonizes phosphatase activation in yeast. Disruption of CNB myristoylation by mutation of the myristoylated glycine triggered constitutive expression of a calcineurin-dependent reporter gene and enhanced calcineurin-dependent phenotypes. Basal phosphatase activity was also increased in nmt1-181 yeast with reduced N-myristoyltransferase activity. Our findings are the first demonstration of a functional role for CNB myristoylation and reveal the importance of Nmt1 in modulating cellular calcineurin activation. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.