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 structural proteins, controlling in this manner multiple cellular functions. In addition to its capacity 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 fine-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 encephalopathies and brain hypoxia, melatonin-regulated neuroendocrine disorders, hypertension, and heavy metal-induced cell toxicity.