Phosphorylation of calmodulin: Functional implications

Journal now known as FEBS Journal.-- Open Access content older than 1 year.Calmodulin (CaM) is phosphorylated in vitro and in vivo by multiple protein-serine/threonine and protein-tyrosine kinases. Casein kinase II and myosin light-chain kinase are two of the well established protein-serine/threonine kinases implicated in this process. On the other hand, within the protein-tyrosine kinases involved in the phosphorylation of CaM are receptors with tyrosine kinase activity, such as the insulin receptor and the epidermal growth factor receptor, and nonreceptor protein-tyrosine kinases, such as several members of the Src family kinases, Janus kinase 2, and p38Syk. The phosphorylation of CaM brings important physiological consequences for the cell as the diverse phosphocalmodulin species have differential actions as compared to nonphosphorylated CaM when acting on different CaM-dependent systems. In this review we will summarize the progress made on this topic as the first report on phosphorylation of CaM was published almost two decades ago. We will emphasize the description of the phosphorylation events mediated by the different protein kinases not only in the test tube but in intact cells, the phosphorylation-mediated changes of CaM activity, its action on CaM-dependent systems, and the functional repercussion of these phosphorylation processes in the physiology of the cell.The work in the authors laboratories was financed by grants from the Comisión Interministerial de Ciencia y Tecnología (SAF99-0052), the Agencia Española de Cooperación Internacional (2002 CN0013) and Consejería de Educación y Cultura de la Comunidad de Madrid (08.1/0027/2001–1) to AV; grants from the Fondo Nacional de Ciencia, Tecnología e Innovación del Ministerio de Ciencia y Tecnología de Venezuela (S1-99000058 and G-2001000637) and Consejo de Desarrollo Científico y Humanístico de la Universidad Central de Venezuela (C-03-10-33-4798/00) to GB; and a grant from the Spanish Ministry of Education (Programa de Cooperación con Iberoamérica) to A. V. and G. B.Peer Reviewe