Protein kinases: starting a molecular systems view of endocytosis

The field of endocytosis is in strong need of formal biophysical modeling and mathematical analysis. At the same time, endocytosis must be much better integrated into cellular physiology to understand the former's complex behavior in such a wide range of phenotypic variations. Furthermore, the concept that endocytosis provides the space-time for signal transduction can now be experimentally addressed. In this review, we discuss these principles and argue for a systematic and top-down approach to study the endocytic membrane system. We provide a summary of published observations on protein kinases regulating endocytic machinery components and discuss global unbiased approaches to further map out kinase regulatory networks. In particular, protein phosphorylation is at the heart of controlling the physical properties of endocytosis and of integrating these physical properties into the signal transduction networks of the cell to allow a fine-tuned response to the continuously varying physiological conditions of a cell.