Preface

A statistical fisherman plumbing the depths of genomic sequences is more likely to land a protein kinase gene than anything else. Since the first of these enzymes was discovered over 35 years ago, estimates of the total number of variants per organism have been steadily upgraded. Current ‘guesstimates’ predict over a thousand, in which case this catalytic unit will represent around 1% of our entire genetic repertoire. What is so unique about this structure to justify such a huge investment in the gene pool? Why are there so many? What do they do and how are they controlled?

The answers to such basic questions are best found by consideration of the family of enzymes as a whole. By definition, all protein kinases are capable of transferring the terminal phosphate group from ATP to an amino acid residue within a protein. However, beyond this shared catalytic process, protein kinases are as diverse in function as they are in phylogenetic distribution. They play a role in virtually all regulatable biological processes, form ion transport to metabolic pathways to DNA replication to differentiation. Their versatility begets their ubiquity and they pervade every area of biology. To counter the sense of over whelming complexity associated with the protein kinase field, one of the aims of this book was to create a manageable resource, a compilation of protein kinase information in an accessible form.

By convention, the book is divided into chapters. However, this segregation serves primarily to identify authors with their contributions. Protein kinases are not easily pigeon holed. By their very nature they affect and are affected by other processes. Therefore, the book’s organization is arbitrary, playing second fiddle to the collection of principles discerned from the study of many different protein kinases that are often equally applicable to others. For example, the structural aspects of this family entered a new era with the elucidation of the first protein kinase crystal structure. Owing to the common thread of structural conservation in the super family, this milestone provide molecular insights in to a variety of areas including the mechanisms by which protein kinase activities are modulated. At the time of writing the structures of three distinct protein kinases have been determined. This will likely increase at a rate comparable to the discovery of new enzymes.