The multifunctional role of phospho-calmodulin in pathophysiological processes.

Calmodulin (CaM) is a versatile Ca²⁺ -sensor/transducer protein that modulates hundreds of enzymes, channels, transport systems, transcription factors, adaptors and other struc- tural proteins, controlling in this manner multiple cellular functions. In addition to its cap- acity to regulate target proteins in a Ca²⁺ -dependent and Ca²⁺ -independent manner, the posttranslational phosphorylation of CaM by diverse Ser/Thr- and Tyr-protein kinases has been recognized as an important additional manner to regulate this protein by fi ne-tuning its functionality. In this review, we shall cover developments done in recent years in which phospho-CaM has been implicated in signalling pathways that are relevant for the onset and progression of diverse pathophysiological processes. These include diverse systems playing a major role in carcinogenesis and tumour development, prion-induced encephal- opathies and brain hypoxia, melatonin-regulated neuroendocrine disorders, hypertension, and heavy metal-induced cell toxicity. [ABSTRACT FROM AUTHOR]