A second calcineurin binding site on the NFAT regulatory domain

• DOI: 10.1073/pnas.97.13.7130
• Publication Date: 2002-07-26T14:35:07Z
• Authors: Sheldon Park; Motonari Uesugi; Gregory L. Verdine
• Keywords: NFAT; Dephosphorylation; Nuclear export signal

NFATc (a member of the family nuclear factors activated T cells) is a transcriptional factor responsible for Ca 2+ -inducible activation cytokine genes during immune response. In resting cells, retained in cytoplasm by mechanism that depends on multiple phosphorylations an N-terminal regulatory domain. Physical interaction with and dephosphorylation -activated calcineurin (Cn) allows protein to enter nucleus, where it binds specific sites gene promoters. Previous studies had identified peptide segment Cn stably. Here we report identification second Cn-binding element NFATc, which synergizes previously element. Although these sequences are conserved all isoforms NFAT, find two contribute differentially overall affinity isoform-dependent manner. The domain NFAT also was found be entirely devoid structure, both phosphorylated unphosphorylated state. This finding suggests does not undergo phosphorylation-induced conformational switching, but instead requires partner proteins control accessibility localization export signals.