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Details on Person Phosphorylation of TBK1 and IKBKE at Ser172 is essential for...

Class:IdSummation:9724212
_displayNamePhosphorylation of TBK1 and IKBKE at Ser172 is essential for...
_timestamp2021-05-20 21:24:43
created[InstanceEdit:9724202] Shamovsky, Veronica, 2021-03-23
literatureReference[LiteratureReference:9724208] PPM1B negatively regulates antiviral response via dephosphorylating TBK1
[LiteratureReference:9731447] PPM1A silences cytosolic RNA sensing and antiviral defense through direct dephosphorylation of MAVS and TBK1
modified[InstanceEdit:9731454] Shamovsky, Veronica, 2021-05-20
textPhosphorylation of TBK1 and IKBKE at Ser172 is essential for the TBK1/IKBKE-mediated antiviral response. Protein phosphatase 1A (PPM1A) was identified as a TBK1/IKBKE phosphatase. (Xiang W et al. 2016). Endogenous complex of PPM1A:TBK1 or PPM1A:IKBKE was detected by coimmunoprecipitation assay using anti-TBK1 or anti-IKBKE antibodies in lysates of human embryonic kidney 293T (HEK293T) cells and visualized by anti-PPM1A antibody (Xiang W et al. 2016). Mass spectrometry analysis further confirmed that endogenous PPM1A was a component of TBK1 complex. Domain mapping analysis performed by coimmunoprecipitation of full-length PPM1A and TBK1 truncations revealed that PPM1A is recruited to the C-terminal kinase domain of TBK1. PPM1A was shown to directly dephosphorylate kinases TBK1 and IKBKE at Ser172. PPM1A can also remove phosphorylation on mitochondria-associated adaptor protein MAVS (Xiang W et al. 2016). Depletion or knockout of PPM1A enhanced antiviral responses in vitro and in vivo (Xiang W et al. 2016). Similarly, PPM1B inhibited Sendai virus (SeV)-induced TBK1-mediated IRF3 activation and IFNβ gene expression in HEK293T cells by targeting and dephosphorylating TBK1 at Ser172 (Zhao Y et al. 2012). PPM1B deficiency increased SeV-induced TBK1 phosphorylation and IFNβ production in HEK293T and HeLa cells compared to control cells (Zhao Y et al. 2012). However, when compared with PPM1A, PPM1B-mediated dephosphorylation of TBK1/IKBKE was weak (Xiang W et al. 2016). Collectively, the data suggest that PPM1A and PPM1B negatively regulates antiviral response downstream of MAVS.

This Reactome event shows PPM1A, PPM1B-mediated dephosphorylation of TBK1 and IKBKE at Ser172.

(summation)[Reaction:9724201] PPM1A, PPM1B dephosphorylate TBK1 or IKBKE [Homo sapiens]
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