Ecto-protein kinases: ecto-domain phosphorylation as a novel target for pharmacological manipulation?

An increasing number of studies document the presence of protein kinases facing outwards at the cell surface of a diverse array of cells. These ecto-protein kinases phosphorylate cell-surface proteins and soluble extracellular substrates, and thus could affect many physiological processes involving cell-cell contacts, cellular differentiation and proliferation, ion fluxes and cellular activation. To date, only limited attention has been paid to exploring ecto-protein kinases as possible pharmacological targets. Here, the identification and physiological role of ecto-protein kinases in different biological systems is described; it is suggested that ecto-protein kinases are attractive and novel candidates for pharmacological manipulation under various (patho)physiological conditions.