p38α MAP kinase phosphorylates RCAN1 and regulates its interaction with calcineurin.

RCAN1, also known as DSCR1, is an endogenous regulator of calcineurin, a serine/threonine protein phosphatase that plays a critical role in many physiological processes. In this report, we demonstrate that p38α MAP kinase can phosphorylate RCAN1 at multiple sites in vitro and show that phospho-RCAN1 is a good protein substrate for calcineurin. In addition, we found that unphosphorylated RCAN1 noncompetitively inhibits calcineurin protein phosphatase activity and that the phosphorylation of RCAN1 by p38α MAP kinase decreases the binding affinity of RCAN1 for calcineurin. These findings reveal the molecular mechanism by which p38α MAP kinase regulates the function of RCAN1/calcineurin through phosphorylation.