Colworth Medal Lecture. Structural studies of reversible protein phosphorylation and protein phosphatases.

Abstract

Introduction The regulation of cellular processes in response to external stimuli is fundamental to all living processes. It is now recognized that the reversible phosphorylation of proteins is an essential element of the numerous and varied mechanisms that have evolved to communicate these stimuli across a cell’s surface, and subsequently to effect changes in the activities and functions of intracellular proteins. Changes in the state of protein phosphorylation are regulated by two types of enzyme activities : the protein kinases, which covalently attach a phosphate group to an amino acid side chain, and the reverse activity of protein phosphatases. Nearly all aspects of cell life are regulated by reversible protein phosphorylation. Many extracellular stimuli, such as hormones, growth factors, cytokines and nerve impulses, regulate cell processes by altering the levels of protein phosphorylation. These processes include cell metabolism, the immune system, cell growth and division, differentiation and development, cytoskeletal reorganization and muscle contraction. Reflecting the diversity and breadth of functions regulated by protein phosphorylation, a large proportion of intracellular proteins (30%) are subject to reversible protein phosphorylation, and it is perhaps