The Coordinated Control of Metabolic Pathways by Broad-Specificity Protein Kinases and Phosphatases

Abstract

This chapter presents some research conducted on the coordinated control of metabolic pathways by broad-specificity protein kinases and phosphatases. The reversible phosphorylation of enzymes is a principal mechanism in the control of almost all metabolic pathways, and in mammalian cells, it may be almost as common as allosteric regulation. Different metabolic pathways may be regulated by the same protein kinases and phosphatases. Cyclic AMP-dependent protein kinase is the second messenger for a large number of hormones and other extracellular signals, which transmit information from plasma membrane receptors to the interior of the cell. Many extracellular signals regulate intracellular events by initiating a transient rise in the cytosolic concentration of Ca 2+ . The Ca 2+ -calmodulin complex is capable of modulating the level of cyclic AMP and activity of cyclic AMP-dependent protein kinase in cells that contain these calmodulin-regulated enzymes. Protein phosphatases present in the cytoplasm of mammalian cells have been classified into two types. In the first type, the protein phosphatases are inhibited by nanomolar concentrations of two thermostable proteins, termed inhibitor 1 and inhibitor 2, and dephosphorylate the subunit of phosphorylase kinase preferentially. In the second type, the protein phosphatases are unaffected by inhibitors 1 and 2 and dephosphorylate the β subunit of phosphorylase kinase preferentially.