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The DSP Domain of Pseudophosphatase MK‐STYX Decreases Stress Granules
Author(s) -
Jiang Fei
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.03315
Subject(s) - stress granule , biology , protein phosphatase 2 , serine , microbiology and biotechnology , mcherry , phosphorylation , phosphatase , protein kinase domain , green fluorescent protein , biochemistry , messenger rna , gene , mutant , translation (biology)
MK‐STYX [MAPK (mitogen activated protein kinase) phosphoserine/threonine/tyrosine binding protein] is a pseudophosphatase. Due to point mutations in the HC(X5)R catalytic active site signature motif, MK‐STYX (FSTQGISR) can only bind, but cannot dephosphorylate phosphorylated residues. This interaction of MK‐STYX allows it to play important roles in various cellular pathways including the stress response pathway. MK‐STYX decreases stress granules (SG) independently of serine 149 phosphorylation of G3BP‐1 (stress granule nucleator). Stress granules are cytoplasmic aggregates of untranslated mRNA and proteins formed in response to stressors. The aim of this study is to determine which domain of MK‐STYX decreases stress granules. MK‐STYX has two domains: a dual specificity phosphatase domain (DSP) and a rhodanese/cdc 25 phosphatase homology domain. In our study, HEK‐293 cells are cotransfected with G3BP‐GFP and mCherry‐DSP, mCherry‐CH2, or mChrerry. Cells expressing G3BP‐GFP and mCherry‐DSP exhibit fewer SG than the control (G3BP‐GFP and mCherry). Whereas, cells cotransfected with G3BP‐GFP and mCherry‐CH2 have similar levels of SG compared to the control, indicating that the DSP domain of MK‐STYX is responsible for decreasing the number of stress granules. Since the “active site” lies within the DSP domain, the study suggests that MK‐STYX decreases SG by binding, and perhaps blocking dephosphorylation of certain proteins. Future studies will focus on characterizing size and exact number of these SGs, as well as the interactors of MK‐STYX‐DSP.