cGAS produces cyclic GMP-AMP

Stable Identifier
R-HSA-3244614
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Human herpesvirus 1, Human immunodeficiency virus 1, Listeria monocytogenes, Mycobacterium tuberculosis
Compartment
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Cyclic dinucleotides (such as c-di-GMP and c-di-AMP) are signaling molecules produced by bacteria. In host cells they are recognized by DNA sensors such as DDX41 and STING to trigger IFN production in a STING-dependent manner (Burdette DL et al. 2011; Yin Q et al. 2012; Parvatiyar K et al. 2012). Cyclic adenosine monophosphate-guanosine monophosphate (cyclic GMP-AMP, cGAMP) has been also implicated in stimulating host responses via STING (Wu J et al. 2013). Chemically synthesized cGAMP was shown to induce IFN-beta production in mouse fibrosarcoma cell line L929 with much higher potency than c-di-GMP and c-di-AMP. Most importantly, cGAMP was identified as the first cyclic di-nucleotide produced by mammalian cells (Wu J et al. 2013). DNA transfection or DNA virus infection of human and mouse cells triggered production of the endogenous second messenger cGAMP, which in turn interacted with STING to activate dimerization of IRF3 and induction of IFN beta (Wu J et al. 2013). cGAMP synthase (cGAS) was reported to catalyze the cGAMP production in the presence of DNA (Sun L et al. 2013). The structural study showed that cGAMP generated by cGAS contains G(2',5')pA and A(3',5')pG phosphodiester linkages, which is distinct from bacterial 3',5' cyclic dinucleotides (Gao P et al. 2013).

Literature References
PubMed ID Title Journal Year
23258413 Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway

Sun, L, Wu, J, Du, F, Chen, X, Chen, ZJ

Science 2013
23258412 Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA

Wu, J, Sun, L, Chen, X, Du, F, Shi, H, Chen, C, Chen, ZJ

Science 2013
Participants
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Catalyst Activity
Catalyst Activity
Title
cyclic-GMP-AMP synthase activity of cGAS:dsDNA [cytosol]
Physical Entity
Activity
Cross References
Rhea
Authored
Reviewed
Created