Phosphorylation by CK2 and MAPK enhances calnexin association with ribosomes.
EMBO J
; 18(13): 3655-66, 1999 Jul 01.
Article
in En
| MEDLINE
| ID: mdl-10393181
ABSTRACT
Calnexin was initially identified as an endoplasmic reticulum (ER) type I integral membrane protein, phosphorylated on its cytosolic domain by ER-associated protein kinases. Although the role of the ER luminal domain of calnexin has been established as a constituent of the molecular chaperone machinery of the ER, less is known about the role of the cytosolic phosphorylation of calnexin. Analysis by two-dimensional phosphopeptide maps revealed that calnexin was in vitro phosphorylated in isolated microsomes by casein kinase 2 (CK2) and extracellular-signal regulated kinase-1 (ERK-1) at sites corresponding to those for in vivo phosphorylation. In canine pancreatic microsomes, synergistic phosphorylation by CK2 and ERK-1 led to increased association of calnexin with membrane-bound ribosomes. In vivo, calnexin-associated ERK-1 activity was identified by co-immunoprecipitation. This activity was abolished in cells expressing a dominant-negative MEK-1. Activation of ERK-1 in cells by addition of serum led to a 4-fold increase in ribosome-associated calnexin over unstimulated cells. Taken together with studies revealing calnexin association with CK2 and ERK-1, a model is proposed whereby phosphorylation of calnexin leads to a potential increase in glycoprotein folding close to the translocon.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ribosomes
/
Calcium-Binding Proteins
/
Protein Serine-Threonine Kinases
/
Calcium-Calmodulin-Dependent Protein Kinases
/
Mitogen-Activated Protein Kinase Kinases
/
Mitogen-Activated Protein Kinases
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
EMBO J
Year:
1999
Document type:
Article