Systems medicine approaches for peptide array-based protein kinase profiling: progress and prospects.

INTRODUCTION

Pharmacological manipulation of signalling pathways is becoming an increasingly important avenue for the rational clinical management of disease but is hampered by a lack of technologies that allow the generation of comprehensive descriptions of cellular signalling.

AREAS COVERED

Herein, the authors discuss the potential of peptide array-based kinome profiling for evaluating cellular signalling in the context of drug discovery. Expert commentary: Genomic and proteomic approaches have been of significant value to our elucidation of the molecular mechanisms that govern physiology. However, an equally, if not more important goal, is to define those proteins that participate in signalling pathways that ultimately control cell fate, especially kinases. Traditional genetic and biochemical approaches can certainly provide answers here, but for technical and practical reasons, are typically pursued one gene or pathway at a time. A more comprehensive approach is one in which peptide arrays of kinase-specific substrates are incubated with cell lysates and (33)P-ATP generating comprehensive descriptions, or where arrays are interrogated with phosphospecific antibodies. Both approaches allow analysis of cellular signalling without a priori assumptions to possibly influenced pathways.