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Tyrosine kinases: the molecular switch for inflammasome activation

Cellular & Molecular Immunology volume 11, pages 129–131 (2014)Cite this article

Inflammasomes are large multiprotein platforms that translate recognition of immune ‘danger' into activation of pro-caspase-1. Caspase-1 in turn proteolytically activates the precursors of the pro-inflammatory cytokines IL-1β and IL-18, which are secreted to support the inflammatory response. The recruitment of pro-caspase-1 to both NLRP3- and absent in melanoma 2 (AIM2)-containing inflammasome complexes is mediated by the apoptosis-associated speck-like protein containing a caspase-recruitment domain (CARD) (ASC). Upon NLRP3 and AIND activation, ASC proteins self-aggregate to form complex structures known as ASC specks, which then recruit pro-caspase-1 through CARD–CARD interactions.1,2

Since ASC is a necessary adaptor molecule for pro-caspase-1 recruitment to NLRP3 and AIM2 inflammasomes, the authors asked whether Syk and Jnk kinases were involved in the NLRP3/ASC or AIM2/ASC interaction. Using an in situ proximity ligation assay, they found that pretreatment of cells with Syk or Jnk inhibitors did not affect ASC/NLRP3 interaction following stimulation with nigericin. However, Syk and Jnk signaling was required for formation of the ASC specks and pro-caspase-1 recruitment in macrophages stimulated with nigericin and poly(dA:dT). Following inflammasome activation, ASC phosphorylation was Syk- and Jnk-dependent, and the authors identified Tyr144 as a putative site of ASC phosphorylation by these kinases (Figure 1). Further experiments will reveal the mechanisms of ASC phosphorylation since there is no clear evidence that Syk or Jnk can phosphorylate ASC directly.

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Figure 1

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Authors and Affiliations

  1. Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore

    Federica Laudisi, Elena ViganĂ²Â & Alessandra Mortellaro

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  1. Federica Laudisi
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  2. Elena ViganĂ²
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  3. Alessandra Mortellaro
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Correspondence to Alessandra Mortellaro.

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Laudisi, F., ViganĂ², E. & Mortellaro, A. Tyrosine kinases: the molecular switch for inflammasome activation. Cell Mol Immunol 11, 129–131 (2014). https://doi.org/10.1038/cmi.2014.4

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