The nuts and bolts of AGC protein kinases

There are 60 members of the AGC family of protein kinases, which all share a conserved catalytic kinase domain.Structural studies have revealed that although the structures of active AGC kinases are highly similar, inactive AGC kinases can adopt several conformations. Most described structures to date are of the catalytic domain; further work is required to elucidate the structure of full length AGC kinases.AGC family members are regulated in various ways, but most require phosphorylation and/or conformational changes to be activated.Functional domains, other than the kinase domain, have important roles in regulating the activity and localization of AGC kinases. The functions of some of these domains have not been fully defined.AGC kinases are involved in numerous cellular processes, exemplified by the large number of proteins that they can phosphorylate. Some substrates are phosphorylated only by one AGC kinase, whereas others can be phosphorylated by multiple AGC kinases.Several AGC family members have been implicated in disease, and numerous drugs targeting these kinases have been developed to treat conditions such as cancer and diabetes. In addition mutations in certain AGC kinases are linked to some inherited syndromes.