期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 12, 页码 4584-4590出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0900774106
关键词
Toll-like receptor; innate immunity; Lysine63-linked polyubiquitination
资金
- U. K. Medical Research Council
- AstraZeneca
- Boehringer Ingelheim
- GlaxoSmithKline
- Merck-Serono
- Pfizer
- Biotechnology and Biological Sciences Research Council
- Medical Research Council
- Wellcome Trust
- Engineering and Physical Sciences Research Council
- Medical Research Council [MC_U127084348] Funding Source: researchfish
- MRC [MC_U127084348] Funding Source: UKRI
The E3 ubiquitin ligase Pellino can be activated by phosphorylation in vitro, catalyzed by IL-1 receptor-associated kinase 1 (IRAK1) or IRAK4. Here, we show that phosphorylation enhances the E3 ligase activity of Pellino 1 similarly with any of several E2-conjugating enzymes (Ubc13-Uev1a, UbcH4, or UbcH5a/5b) and identify 7 amino acid residues in Pellino 1 whose phosphorylation is critical for activation. Five of these sites are clustered between residues 76 and 86 (Ser-76, Ser-78, Thr-80, Ser-82, and Thr-86) and decorate a region of antiparallel beta-sheet, termed the wing,'' which is an appendage of the forkhead-associated domain that is thought to interact with IRAK1. The other 2 sites are located at Thr-288 and Ser-293, just N-terminal to the RING-like domain that carries the E3 ligase activity. Unusually, the full activation of Pellino 1 can be achieved by phosphorylating any one of several different sites (Ser-76, Thr-86, Thr-288, or Ser-293) or a combination of other sites (Ser-78, Thr-80, and Ser-82). These observations imply that dephosphorylation of multiple sites is required to inactivate Pellino 1, which could be a device for prolonging Pellino's E3 ubiquitin ligase activity in vivo.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据