Ca2+-dependent Cell Signaling through Calmodulin-activated Protein Phosphatase and Protein Kinases Minireview Series

Over 100 years ago Sydney Ringer first showed that extracellular Ca2+ was necessary for muscle contractions (1). Research during the past 50 years has revealed that intracellular Ca2+ mediates a large number of cellular responses with the high affinity and specificity required for a regulatory second messenger. The identification and biochemical characterization of Ca2+-dependent signaling pathways were stimulated by the pioneering proposal that Ca2+ acts by binding to specific intracellular proteins, which may be considered Ca2+ receptors (2).