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A tale of two proteins: PACT and PKR and their roles in inflammation
Author(s) -
Chukwurah Evelyn,
Farabaugh Kenneth T.,
Guan BoJhih,
Ramakrishnan Parameswaran,
Hatzoglou Maria
Publication year - 2021
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15691
Subject(s) - protein kinase r , inflammation , proinflammatory cytokine , pact , signal transduction , biology , interferon , activator (genetics) , microbiology and biotechnology , protein kinase a , receptor , kinase , immunology , genetics , mitogen activated protein kinase kinase , history , archaeology
Inflammation is a pathological hallmark associated with bacterial and viral infections, autoimmune diseases, genetic disorders, obesity and diabetes, as well as environmental stresses including physical and chemical trauma. Among numerous proteins regulating proinflammatory signaling, very few such as Protein kinase R (PKR), have been shown to play an all‐pervading role in inflammation induced by varied stimuli. PKR was initially characterized as an interferon‐inducible gene activated by viral double‐stranded RNA with a role in protein translation inhibition. However, it has become increasingly clear that PKR is involved in multiple pathways that promote inflammation in response to stress activation, both dependent on and independent of its cellular protein activator of PKR (PACT). In this review, we discuss the signaling pathways that contribute to the initiation of inflammation, including Toll‐like receptor, interferon, and RIG‐I‐like receptor signaling, as well as inflammasome activation. We go on to discuss the specific roles that PKR and PACT play in such proinflammatory signaling, as well as in metabolic syndrome‐ and environmental stress‐induced inflammation.