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[[File:2'3'-cGAMP.jpg|thumb|cyclic GMP-AMP structure]]
[[File:2'3'-cGAMP.jpg|thumb|cyclic GMP-AMP structure]]
'''Cyclic guanosine monophosphate–adenosine monophosphate''' (cyclic GMP-AMP, cGAMP) is the first [[cyclic di-nucleotide]] found in [[metazoa]].<ref name=Gao>{{cite journal|last=Gao|first=P|coauthors=Ascano, M; Wu, Y; Barchet, W; Gaffney, BL et al|title=Cyclic [G(2′,5′)pA(3′,5′)p] Is the Metazoan Second Messenger Produced by DNA-Activated Cyclic GMP-AMP Synthase|journal=Cell|date=May 3, 2013|volume=153|issue=5|pages=1094–1107|doi=10.1016/j.cell.2013.04.046}}</ref><ref name="pmid23258412">{{cite journal|last=Wu|first=J|coauthors=Sun, L; Chen, X; Du, F; Shi, H; Chen, C; Chen, ZJ|title=Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA.|journal=Science|date=Dec 20, 2012|volume=339|issue=6121|pages=826–30|pmid=23258412|doi=10.1126/science.1229963}}</ref>
'''Cyclic guanosine monophosphate–adenosine monophosphate''' (cyclic GMP-AMP, cGAMP) is the first [[cyclic di-nucleotide]] found in [[metazoa]].<ref name="pmid23258412">{{cite journal|last=Wu|first=J|coauthors=Sun, L; Chen, X; Du, F; Shi, H; Chen, C; Chen, ZJ|title=Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA.|journal=Science|date=Dec 20, 2012|volume=339|issue=6121|pages=826–30|pmid=23258412|doi=10.1126/science.1229963}}</ref>
In mammalian cells, cGAMP is synthesized by [[cyclic GMP-AMP synthase]] ([[cyclic GMP-AMP synthase|cGAS]]) from [[Adenosine triphosphate|ATP]] and [[Guanosine triphosphate|GTP]] upon cytosolic DNA stimulation.<ref>{{cite journal|last=Sun|first=L|coauthors=Wu, J; Du, F; Chen, X; Chen, ZJ|title=Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway|journal=Science|date=Dec 20, 2012|volume=339|issue=6121|pages=786–91|pmid=23258413|doi=10.1126/science.1232458}}</ref> cGAMP produced by cGAS contains mixed phosphodiester linkages, with one between 2'-OH of GMP and 5'-phosphate of AMP and the other between 3'-OH of AMP and 5'-phosphate of GMP.<ref name=Zhang>{{cite journal|last=Zhang|first=X|coauthors=Shi, H; Wu, J; Zhang, X; Sun, L; Chen, C; Chen, ZJ|title=Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High-Affinity Ligand for STING|journal=Molecular Cell|date=Jun 3, 2013|volume=51|issue=2|pages=226–235|doi=10.1016/j.molcel.2013.05.022}}</ref><ref name=Gao>{{cite journal|last=Gao|first=P|coauthors=Ascano, M; Wu, Y; Barchet, W; Gaffney, BL et al|title=Cyclic [G(2′,5′)pA(3′,5′)p] Is the Metazoan Second Messenger Produced by DNA-Activated Cyclic GMP-AMP Synthase|journal=Cell|date=May 3, 2013|volume=153|issue=5|pages=1094–1107|doi=10.1016/j.cell.2013.04.046}}</ref><ref name=Ablasser>{{cite journal|last=Ablasser|first=A|coauthors=Goldeck, M; Cavlar, T; Deimling, T; Witte, G; Röhl, I; Hopfner, KP; Ludwig, J; Hornung, V|title=cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING|journal=Nature|date=Jun 20, 2013|volume=498|issue=7454|pages=380–384|doi=10.1038/nature12306}}</ref><ref name=Diner>{{cite journal|last=Diner|first=EJ|coauthors=Burdette, DL; Wilson, SC; Monroe, KM; Kellenberger, CA; Hyodo, M; Hayakawa, Y; Hammond, MC; Vance, RE|title=The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING|journal=Cell Reports|date=May 23, 2013|volume=3|issue=5|pages=1355–61|doi=10.1016/j.celrep.2013.05.009}}</ref> This molecule,referred to as 2′3′-cGAMP (cyclic [G(2’,5’)pA(3’,5’)p]), functions as an endogenous [[second messenger]] inducing STING-dependent [[Interferon type I|type I interferon]] response.<ref name="pmid23258412"/><ref name=Zhang/> cGAMP has also been shown to be an effective adjuvant that boosts the production of antigen-specific antibodies and T cell responses in mice.<ref name=Li>{{cite journal|last=Li|first=XD|coauthors=Wu, J; Gao, D; Wang, H; Sun, L; Chen, ZJ|title=Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects|journal=Science|date=Sep 20, 2013|volume=341|issue=6152|pages=1390–4|doi=10.1126/science.1244040}}</ref>
In mammalian cells, cGAMP is synthesized by [[cyclic GMP-AMP synthase]] ([[cyclic GMP-AMP synthase|cGAS]]) from [[Adenosine triphosphate|ATP]] and [[Guanosine triphosphate|GTP]] upon cytosolic DNA stimulation.<ref>{{cite journal|last=Sun|first=L|coauthors=Wu, J; Du, F; Chen, X; Chen, ZJ|title=Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway|journal=Science|date=Dec 20, 2012|volume=339|issue=6121|pages=786–91|pmid=23258413|doi=10.1126/science.1232458}}</ref> cGAMP produced by cGAS contains mixed phosphodiester linkages, with one between 2'-OH of GMP and 5'-phosphate of AMP and the other between 3'-OH of AMP and 5'-phosphate of GMP.<ref name=Zhang>{{cite journal|last=Zhang|first=X|coauthors=Shi, H; Wu, J; Zhang, X; Sun, L; Chen, C; Chen, ZJ|title=Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High-Affinity Ligand for STING|journal=Molecular Cell|date=Jun 3, 2013|volume=51|issue=2|pages=226–235|doi=10.1016/j.molcel.2013.05.022}}</ref><ref name=Gao>{{cite journal|last=Gao|first=P|coauthors=Ascano, M; Wu, Y; Barchet, W; Gaffney, BL et al|title=Cyclic [G(2′,5′)pA(3′,5′)p] Is the Metazoan Second Messenger Produced by DNA-Activated Cyclic GMP-AMP Synthase|journal=Cell|date=May 3, 2013|volume=153|issue=5|pages=1094–1107|doi=10.1016/j.cell.2013.04.046}}</ref><ref name=Ablasser>{{cite journal|last=Ablasser|first=A|coauthors=Goldeck, M; Cavlar, T; Deimling, T; Witte, G; Röhl, I; Hopfner, KP; Ludwig, J; Hornung, V|title=cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING|journal=Nature|date=Jun 20, 2013|volume=498|issue=7454|pages=380–384|doi=10.1038/nature12306}}</ref><ref name=Diner>{{cite journal|last=Diner|first=EJ|coauthors=Burdette, DL; Wilson, SC; Monroe, KM; Kellenberger, CA; Hyodo, M; Hayakawa, Y; Hammond, MC; Vance, RE|title=The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING|journal=Cell Reports|date=May 23, 2013|volume=3|issue=5|pages=1355–61|doi=10.1016/j.celrep.2013.05.009}}</ref> This molecule,referred to as 2′3′-cGAMP (cyclic [G(2’,5’)pA(3’,5’)p]), functions as an endogenous [[second messenger]] inducing STING-dependent [[Interferon type I|type I interferon]] response.<ref name="pmid23258412"/><ref name=Zhang/> cGAMP has also been shown to be an effective adjuvant that boosts the production of antigen-specific antibodies and T cell responses in mice.<ref name=Li>{{cite journal|last=Li|first=XD|coauthors=Wu, J; Gao, D; Wang, H; Sun, L; Chen, ZJ|title=Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects|journal=Science|date=Sep 20, 2013|volume=341|issue=6152|pages=1390–4|doi=10.1126/science.1244040}}</ref>


Revision as of 05:04, 27 May 2014

cyclic GMP-AMP structure

Cyclic guanosine monophosphate–adenosine monophosphate (cyclic GMP-AMP, cGAMP) is the first cyclic di-nucleotide found in metazoa.[1] In mammalian cells, cGAMP is synthesized by cyclic GMP-AMP synthase (cGAS) from ATP and GTP upon cytosolic DNA stimulation.[2] cGAMP produced by cGAS contains mixed phosphodiester linkages, with one between 2'-OH of GMP and 5'-phosphate of AMP and the other between 3'-OH of AMP and 5'-phosphate of GMP.[3][4][5][6] This molecule,referred to as 2′3′-cGAMP (cyclic [G(2’,5’)pA(3’,5’)p]), functions as an endogenous second messenger inducing STING-dependent type I interferon response.[1][3] cGAMP has also been shown to be an effective adjuvant that boosts the production of antigen-specific antibodies and T cell responses in mice.[7]

References

  1. ^ a b Wu, J (Dec 20, 2012). "Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA". Science. 339 (6121): 826–30. doi:10.1126/science.1229963. PMID 23258412. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  2. ^ Sun, L (Dec 20, 2012). "Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway". Science. 339 (6121): 786–91. doi:10.1126/science.1232458. PMID 23258413. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  3. ^ a b Zhang, X (Jun 3, 2013). "Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High-Affinity Ligand for STING". Molecular Cell. 51 (2): 226–235. doi:10.1016/j.molcel.2013.05.022. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  4. ^ Gao, P (May 3, 2013). "Cyclic [G(2′,5′)pA(3′,5′)p] Is the Metazoan Second Messenger Produced by DNA-Activated Cyclic GMP-AMP Synthase". Cell. 153 (5): 1094–1107. doi:10.1016/j.cell.2013.04.046. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  5. ^ Ablasser, A (Jun 20, 2013). "cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING". Nature. 498 (7454): 380–384. doi:10.1038/nature12306. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  6. ^ Diner, EJ (May 23, 2013). "The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING". Cell Reports. 3 (5): 1355–61. doi:10.1016/j.celrep.2013.05.009. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  7. ^ Li, XD (Sep 20, 2013). "Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects". Science. 341 (6152): 1390–4. doi:10.1126/science.1244040. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
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