Inducible Priming Phosphorylation Promotes Ligand-independent Degradation of the IFNAR1 Chain of Type I Interferon Receptor
| Autor: | Sudhakar Veeranki, J. Alan Diehl, Wei Chun HuangFu, Darren P. Baker, Sabyasachi Bhattacharya, Constantinos Koumenis, Serge Y. Fuchs, Jianghuai Liu |
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| Rok vydání: | 2010 |
| Předmět: |
Ubiquitin-Protein Ligases
Molecular Sequence Data Receptor Interferon alpha-beta Ligands Biochemistry Mice eIF-2 Kinase Interferon medicine Animals Humans Immunologic Factors Amino Acid Sequence Phosphorylation Molecular Biology Conserved Sequence biology Casein Kinase I Kinase Endoplasmic reticulum Mechanisms of Signal Transduction Ubiquitination Interferon-alpha Interferon-beta Cell Biology Fibroblasts Ubiquitin ligase Unfolded Protein Response biology.protein Unfolded protein response Casein kinase 1 Degron HeLa Cells Signal Transduction medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 285:2318-2325 |
| ISSN: | 0021-9258 |
| Popis: | Phosphorylation-dependent ubiquitination and ensuing down-regulation and lysosomal degradation of the interferon alpha/beta receptor chain 1 (IFNAR1) of the receptor for Type I interferons play important roles in limiting the cellular responses to these cytokines. These events could be stimulated either by the ligands (in a Janus kinase-dependent manner) or by unfolded protein response (UPR) inducers including viral infection (in a manner dependent on the activity of pancreatic endoplasmic reticulum kinase). Both ligand-dependent and -independent pathways converge on phosphorylation of Ser(535) within the IFNAR1 degron leading to recruitment of beta-Trcp E3 ubiquitin ligase and concomitant ubiquitination and degradation. Casein kinase 1 alpha (CK1 alpha) was shown to directly phosphorylate Ser(535) within the ligand-independent pathway. Yet given the constitutive activity of CK1 alpha, it remained unclear how this pathway is stimulated by UPR. Here we report that induction of UPR promotes the phosphorylation of a proximal residue, Ser(532), in a pancreatic endoplasmic reticulum kinase-dependent manner. This serine serves as a priming site that promotes subsequent phosphorylation of IFNAR1 within its degron by CK1 alpha. These events play an important role in regulating ubiquitination and degradation of IFNAR1 as well as the extent of Type I interferon signaling. |
| Databáze: | OpenAIRE |
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