title: Calnexin phosphorylation: linking cytoplasmic signalling to endoplasmic reticulum lumenal functions.
abstract: Calnexin is an abundant integral membrane phosphoprotein of the endoplasmic reticulum (ER) of eukaryotic cells. The role of the luminal domain as an N-glycoprotein specific lectin has been well-established. Cytosolic C-terminal domain phosphorylation of calnexin has recently been elucidated in glycoprotein folding and quality control. Signalling of the presence of unfolded proteins from the lumen of the ER is mediated by the three ER membrane sensor proteins Ire1, ATF6 and PERK. The observation that the C-terminus of calnexin is differentially phosphorylated when glycoproteins are misfolded initiated our search for functional roles of calnexin phosphorylation. Recent studies have defined a role for phosphorylation at a proline-directed kinase site (Ser563) in ER protein quality control, while phosphorylation at a casein kinase 2 site (Ser534, Ser544) may be linked to transport functions. There are also four other abundant integral membrane phosphoproteins in the ER, and these may be components of other signalling pathways that link and coordinate other ER functions with the rest of the cell.
authors.affiliation: Avenir, INSERM U889, Université Victor Segalen Bordeaux 2, F-33076 Bordeaux, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Chevet
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Smirle
authors.forename: Pamela H
authors.initials: PH
authors.lastname: Cameron
authors.forename: David Y
authors.initials: DY
authors.lastname: Thomas
authors.forename: John J M
authors.initials: JJ
authors.lastname: Bergeron
mesh_terms: D000818:Animals; D037281:Calnexin / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D015388:Organelles / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D006023:Glycoproteins; D037102:Lectins; D010750:Phosphoproteins; D037281:Calnexin; D047390:Casein Kinase II