Calnexin phosphorylation: linking cytoplasmic signalling to endoplasmic reticulum lumenal functions.
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.
Chevet
Eric
E
Avenir, INSERM U889, Université Victor Segalen Bordeaux 2, F-33076 Bordeaux, France.
Smirle
Jeffrey
J
Cameron
Pamela H
PH
Thomas
David Y
DY
Bergeron
John J M
JJ
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
D006023:Glycoproteins; D037102:Lectins; D010750:Phosphoproteins; D037281:Calnexin; D047390:Casein Kinase II