Calmodulin: effects of cell stimuli and drugs on cellular activation.

The activity, localization and cellular content of CaM can be regulated by drugs, hormones and neurotransmitters. Regulation of physiological responses of CaM can depend upon local Ca(2+)-entry domains in the cells and phosphorylation of CaM target proteins, which would either decrease responsiveness of CaM target enzymes or increase CaM availability for binding to other target proteins. Despite the abundance of CaM in many cells, persistent cellular activation by a variety of substances can lead to an increase in CaM, reflected both in the nucleus and other cellular compartments. Increases in CaM-binding proteins can accompany stimuli-induced increases in CaM. A role for CaM in vesicular or protein transport, cell morphology, secretion and other cytoskeletal processes is emerging through its binding to cytoskeletal proteins and myosins in addition to the more often investigated activation of target enzymes. More complete knowledge of the physiological regulation of CaM can lead to a greater understanding of its role in physiological processes and ways to alter its actions through pharmacology.