HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Molecular cloning and functional characterization of porcine cyclic GMP-AMP synthase.

Abstract
Cyclic GMP-AMP synthase (cGAS), which belongs to the nucleotidyltransferase family, recognizes cytosolic DNA and induces the type I interferon (IFN) pathway through the synthesis of the second messenger cGAMP. In this study, porcine cGAS (p-cGAS) was identified and its tissue distribution, subcellular localization, and functions in innate immunity were characterized. The coding sequence of p-cGAS is 1494 bp long, encodes 497 amino acids, and is most similar (74%) to Bos taurus cGAS. p-cGAS mRNA is abundant in the spleen, duodenum, jejunum, and ileum. The subcellular distribution of p-cGAS is not only in the cytosol, but also on the endoplasmic reticulum (ER) membrane. The overexpression of wild-type p-cGAS in porcine kidney epithelial cells, but not its catalytically inactive mutants, induced IFN-β expression, which was dependent on STING and IRF3. However, the downregulation of p-cGAS by RNA interference markedly reduced IFN-β expression after pseudorabies virus (PRV) infection or poly(dA:dT) transfection. These results demonstrate that p-cGAS is an important DNA sensor, required for IFN-β activation.
AuthorsJiang Wang, Beibei Chu, Lili Du, Yingqian Han, Xuemei Zhang, Shuangshuang Fan, Yueying Wang, Guoyu Yang
JournalMolecular immunology (Mol Immunol) Vol. 65 Issue 2 Pg. 436-45 (Jun 2015) ISSN: 1872-9142 [Electronic] England
PMID25765883 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Ltd. All rights reserved.
Chemical References
  • Poly dA-dT
  • Interferon-beta
  • Nucleotidyltransferases
Topics
  • Amino Acid Sequence
  • Animals
  • Cattle
  • Cloning, Molecular
  • Endoplasmic Reticulum (genetics, immunology)
  • Gene Expression Regulation (immunology)
  • Interferon-beta (genetics, immunology)
  • Intracellular Membranes (immunology)
  • Molecular Sequence Data
  • Mutation
  • Nucleotidyltransferases (genetics, immunology)
  • Organ Specificity (genetics, immunology)
  • Poly dA-dT (pharmacology)
  • Sequence Homology, Amino Acid
  • Swine (genetics, immunology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: