PKC and the control of localized signal dynamics

Key Points The protein kinase C (PKC) family of lipid-activated protein kinases lend themselves to compartmentalized action, a property of signalling systems that is increasingly recognized as crucial in determining dynamic cellular behaviour. The Review exemplifies how PKC isoforms can influence such localized signals. The modular nature of PKCs allows PKC activity to be deployed with spatial and temporal specificity. It also allows PKC activity to be directed by multiple inputs, including localized (membrane limited) second messenger production and interaction with membrane-anchored small G proteins, scaffolds and accessory proteins. The relationship between PKC action and associated signalling events in cell–cell interaction are exemplified by the roles of PKCθ in the interaction of T cells with peptide-bound antigen-presenting cells, as well as the role of atypical PKCs (aPKCs) in cell polarity. The localized behaviour of signals under PKC control are illustrated by particular examples of migratory behaviour, including MET-dependent migration involving PKCα and PKCɛ, and aPKC-dependent migration. Our ability to locally interfere with signals to provide evidence of necessity and sufficiency has been limited by a lack of appropriate experimental methodologies. Strategies are necessary that allow the manipulation of spatial and dynamic behaviour in a physiological context. The protein kinase C (PKC) family has been increasingly implicated in the organization of signal propagation, particularly in the spatial distribution of signals. Examples of where and how various PKC isoforms direct this tier of signal organization are becoming more evident. Networks of signal transducers determine the conversion of environmental cues into cellular actions. Among the main players in these networks are protein kinases, which can acutely and reversibly modify protein functions to influence cellular events. One group of kinases, the protein kinase C (PKC) family, have been increasingly implicated in the organization of signal propagation, particularly in the spatial distribution of signals. Examples of where and how various PKC isoforms direct this tier of signal organization are becoming more evident.