Editors' ChoiceCalcium signaling

Regulator of Calcium Signaling

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Science's STKE  26 Oct 2004:
Vol. 2004, Issue 256, pp. tw386
DOI: 10.1126/stke.2562004tw386

Many calcium-dependent signals are mediated by the calcium sensor protein calmodulin. Rakhilin et al. describe a calmodulin-binding protein that appears to function at the interface of two major signaling pathways activated by G protein-coupled receptors--one mediated by the cyclic adenosine monophosphate-dependent protein kinase (PKA) and the other by phospholipase C and intracellular calcium signals. Alterations in signaling by such receptors are associated with a number of major diseases of the nervous system. This protein, called RCS for regulator of calcium signaling, bound to and inhibited calmodulin. RCS binding to calmodulin was enhanced when RCS was phosphorylated by PKA. Phosphorylated RCS inhibited activity of the calcium/calmodulin-dependent protein phosphatase (PP2B). Phosphorylated RCS is thus poised both to enhance signaling through PKA (because substrates of PKA are often dephosphorylated by PP2B) and, at the same time, to inhibit the action of calmodulin, promoting a range of calcium-dependent signals.

S. V. Rakhilin, P. A. Olson, A. Nishi, N. N. Starkova, A. A. Fienberg, A. C. Nairn, D. J. Surmeier, P. Greengard, A network of control mediated by regulator of calcium/calmodulin-dependent signaling. Science 306, 698-701 (2004). [Abstract] [Full Text]

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