Cross-talk between calcium and protein kinase A in the regulation of cell migration.

Calcium (Ca(2+)) and the cAMP-dependent protein kinase (PKA) are pleiotropic cellular regulators and both exert powerful, diverse effects on cytoskeletal dynamics, cell adhesion, and cell migration. Localization, by A-kinase-anchoring proteins (AKAPs), of PKA activity to the protrusive leading edge, integrins, and other regulators of cytoskeletal dynamics has emerged as an important facet of its role in cell migration. Additional recent work has firmly established the importance of Ca(2+) influx through mechanosensitive transient receptor potential (TRP) channels and through store-operated Ca(2+) entry (SOCE) in cell migration. Finally, there is considerable evidence showing that these mechanisms of Ca(2+) influx and PKA regulation intersect--and often interact--and thus may work in concert to translate complex extracellular cues into the intracellular biochemical anisotropy required for directional cell migration.