Targeting of PKA in mammary epithelial cells. Mechanisms and functional consequences

Targeting of protein kinases, promoting association with specific partner-molecules and localisation to particular sites within the cell, has come to be recognised as a key mechanism for attributing specificity to these enzymes. In mammary epithelial cells, the repertoire of acute regulatory roles played by cyclic AMP-dependent protein kinase (PKA) differs from that in other lipogenic cell-types. Furthermore, PKA is implicated in the regulation of mammary-specific function, mediating a tonic stimulation of the flux of newly-synthesised casein through its basal secretory pathway. Both these observations imply mammary-specific properties of either PKA targeting systems or of PKA itself. Evidence for the latter is currently lacking. Pulse-chase labelling experiments in the presence and absence of selective effectors of PKA have enabled the site(s) of action of this protein kinase on casein secretion to be localised to the early stages of the secretory pathway. Possible mechanisms are considered for the physical targeting of PKA to the membrane-enclosed components of the secretory pathway and evidence for their occurrence in mammary epithelial cells is presented.