Calcineurin interacts with PERK and dephosphorylates calnexin to relieve ER stress in mammals and frogs.

ABSTRACT:

Background

The accumulation of misfolded proteins within the endoplasmic reticulum (ER) triggers a cellular process known as the Unfolded Protein Response (UPR). One of the earliest responses is the attenuation of protein translation. Little is known about the role that Ca2+ mobilization plays in the early UPR. Work from our group has shown that cytosolic phosphorylation of calnexin (CLNX) controls Ca2+ uptake into the ER via the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) 2b.

Methodology/principal findings

Here, we demonstrate that calcineurin (CN), a Ca2+ dependent phosphatase, associates with the (PKR)-like ER kinase (PERK), and promotes PERK auto-phosphorylation. This association, in turn, increases the phosphorylation level of eukaryotic initiation factor-2 alpha (e

SUBMITTER: Bollo M 

PROVIDER: S-EPMC2916823 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature