|
Calcineurin is a phosphoprotein phosphatase that channels intracellular Ca
signals into multiple biological pathways. Calcineurin is known to interact
directly with its substrate nuclear factor of activated T cells (NFAT or NFATc),
with other substrates, and with several targeting and scaffold proteins
including AKAP79 and Cabin1/cain. The calcineurin-NFAT interaction depends on
recognition of a PxIxIT sequence motif present in NFAT-family proteins and in
certain other calcineurin-interacting proteins. Here, we define the structural
basis for the interaction of calcineurin with NFAT and with other proteins
possessing the PxIxIT motif. The calcineurin-PxIxIT contact has a direct
parallel in the contact of protein phosphatase 1 with its regulatory proteins,
suggesting that the evolution of these related phosphatases involved local
remodelling of an ancestral docking site.
|
