Structure, Regulation, and Function of Calcium/Calmodulin-Dependent Protein Kinase I

Abstract

Publisher Summary In particular, a large number of the effects of Ca2+/CaM are mediated through the regulation of protein phosphorylation and dephosphorylation. A family of Ca2+/CaM-dependent protein kinases (CaM kinases) has been identified. The first two members identified, myosin light-chain kinase (MLCK) and phosphorylase kinase, were found to be highly specific for their respective substrates, myosin P light chain and phosphorylase. This led to the initial belief that the CaM kinases were monofunctional kinases that were distinct from the multifunctional protein kinases such as CAMP-dependent protein kinase (PKA) or protein kinase C (PKC). The CaM kinases share many common features. They each have a highly conserved catalytic domain and a COOH-terminal regulatory domain that is not as highly conserved among family members. In addition, several of the enzymes have NH 2 - and/or COOH-terminal extensions that are involved in interaction with other subunits or in targeting to specific subcellular locations. Irrespective of the exact relationship of CaM kinase W and CaM kinases Ia and Ib, CaM kinase I is the smallest member of the CaM kinase family. Based on extensive biochemical and structural analyses of the CaM kinases, as well as other second messenger-regulated protein kinases, it has been proposed that this class of enzyme is regulated by an intrasteric autoinhibitory mechanism. The central feature of this mechanism is that amino acid residues within the regulatory domain bind to the active site of the kinase and sterically block the access of peptide substrate and/ or MgATP.