Inducible priming phosphorylation promotes ligand-independent degradation of the IFNAR1 chain of Type I interferon receptor

Sabyasachi Bhattacharya, Wei Chun HuangFu, Jianghuai Liu, Sudhakar Veeranki, Darren P. Baker, Constantinos Koumenis, J. Alan Diehl, Serge Y. Fuchs

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38 引文 斯高帕斯(Scopus)

摘要

Phosphorylation-dependent ubiquitination and ensuing down-regulation and lysosomal degradation of the interferon α/β 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 Ser535 within the IFNAR1 degron leading to recruitment of β-Trcp E3 ubiquitin ligase and concomitant ubiquitination and degradation. Casein kinase 1α (CK1α) was shown to directly phosphorylate Ser535 within the ligand-independent pathway. Yet given the constitutive activity of CK1α, 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 CK1α. These events play an important role in regulating ubiquitination and degradation of IFNAR1 as well as the extent of Type I interferon signaling.
原文英語
頁(從 - 到)2318-2325
頁數8
期刊Journal of Biological Chemistry
285
發行號4
DOIs
出版狀態已發佈 - 一月 22 2010
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 分子生物學
  • 細胞生物學

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