Calcineurin: a central controller of signalling in eukaryotes

Abstract

Workshop on the Calcium/Calcineurin/NFAT Pathway: Regulation and Function

Figure 1

Signal integration and coincidence detection by assembly of NFATc transcriptional complexes in the nucleus. A range of signalling pathways are integrated in the nucleus by the assembly of NFATc transcriptional complexes from calcineurin-dependent NFATc subunits and inducible nuclear partners (NFATn), which regulate the affinity and specificity of NFATc DNA binding and ensure transcriptional activation in response to two signals. This mechanism allows the complexes to behave as coincidence detectors and signal integrators. CK1, casein kinase 1; Csp1, calcipressin 1; DSCR1, Down syndrome critical region 1; Erk, extracellular-signal-regulated kinase; GSK3, glycogen synthase kinase 3; MCIP1, myocyte-enriched calcineurin interacting protein 1; NFAT, nuclear factor of activated T cells; PKA, protein kinase A; PKC, protein kinase C; RCN1, regulator of calcineurin 1.

Figure 2

Reciprocal NFATc2, c3 and c4 signalling in angiogenesis and endothelial migration. Local signals lead to the activation of NFATc3 and c4, and the inhibition of VEGF production (Graef et al, 2001) as well as, possibly, the synthesis of anti-angiogenic factors. Later in development, VEGF signalling requires NFATc2 in endothelial cells to activate COX2 and to lead to the migration of endothelial cells (Hernandez et al, 2001). Cn, calcineurin; COX2, cyclo-oxygenase 2; NFAT, nuclear factor of activated T cells; VEGF, vascular endothelial growth factor.

This meeting took place at the Juan March Foundation, Madrid, Spain, between 3 and 5 November 2003. It was sponsored by the Juan March Foundation and organized by E. Olson and J.M. Redondo.