Exit of major histocompatibility complex class II-invariant chain p35 complexes from the endoplasmic reticulum is modulated by phosphorylation.
The Iip35 isoform of the major histocompatibility complex (MHC) class II-associated invariant chain (Ii) contains an endoplasmic reticulum (ER) targeting motif, but in B cell lines the ER retention is ineffective and a fraction of Iip35 is transported through the Golgi complex associated with class II molecules. We found Iip35 (but not Iip33, the major form of Ii) to be phosphorylated in B cell lines, as well as in transfected HeLa cells. The phosphorylation of Iip35 was found to be necessary for the exit of Iip35-class II complexes out of the ER. This requirement suggests that phosphorylation may change the interaction with factors responsible for ER retention/retrieval, and we did find that phosphorylated Iip35 associates with 14-3-3 proteins, a family of adaptor proteins that are involved in coordinating signal transduction pathways. This finding raises the intriguing possibility that the exit of Ii-class II complexes from the ER is regulated by intracellular signaling events.
Kuwana
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The R. W. Johnson Pharmaceutical Research Institute, 3535 General Atomics Court, Suite 100, San Diego, CA 92121, USA.
Peterson
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Karlsson
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D048948:14-3-3 Proteins; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism; D034281:Dynamins; D015180:Electrophoresis, Gel, Two-Dimensional; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006367:HeLa Cells; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D053219:Receptors, Tumor Necrosis Factor, Member 25; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase
D048948:14-3-3 Proteins; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000951:Antigens, Neoplasm; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D053219:Receptors, Tumor Necrosis Factor, Member 25; C506033:TNFRSF25 protein, human; C045084:invariant chain; D012694:Serine; D014446:Tyrosine 3-Monooxygenase; D020558:GTP Phosphohydrolases; D034281:Dynamins