1001 Protein Kinases Redux—Towards 2000

Abstract

Recent genomic analysis indicates that the number of protein kinase genes in eukaryotes may be higher than previously thought, and vertebrate genomes may contain in the vicinity of 2000. In addition to the growing protein-serine/protein-tyrosine kinase superfamily, new types of protein kinase have been discovered that operate on different structural principles. The structures of four protein-serine kinases have been solved and have revealed a common structural core containing the highly conserved residues in the catalytic domain. These structures provide insights into substrate selectivity and protein kinase activation. New regulatory principles for protein kinases have been uncovered, including phosphorylation of residues within the catalytic domain by a second protein kinase, new second messengers and specific protein inhibitors. Evidence that protein kinase cascades play an important role in signal transduction has emerged. A number of fundamental cellular processes such as the cell cycle and transcription have been shown to require protein phosphorylation.