A crucial role for the phosphorylation of STRAP at Ser188by MPK38 in STRAP-dependent cell death through ASK1, TGF-β, p53, and PI3K/PDK1 signaling pathways
Copyright policy )A crucial role for the phosphorylation of STRAP at Ser188by MPK38 in STRAP-dependent cell death through ASK1, TGF-β, p53, and PI3K/PDK1 signaling pathways
Serine-threonine kinase receptor-associated protein (STRAP) is a TGF-β receptor-interacting protein that participates in the regulation of cell proliferation and cell death in response to various stresses. Here, we demonstrate that STRAP phosphorylation plays an important role in determining the pro- or anti-apoptotic function of STRAP. Murine protein serine/threonine kinase 38 (MPK38) phosphorylates STRAP at Ser(188) via direct interaction. Complex formation between STRAP and MPK38 is mediated by Cys(152) and Cys(270) of STRAP and Cys(339) and Cys(377) of MPK38, suggesting the redox dependency of this interaction. MPK38-mediated STRAP Ser(188) phosphorylation contributes to the pro-apoptotic function of STRAP by modulating key steps in STRAP-dependent ASK1, TGF-β, p53, and PI3K/PDK1 signaling pathways. Moreover, knockdown of endogenous MPK38 using an inducible MPK38 shRNA system and in vivo activation of MPK38 by treatment of HEK293 and STRAP-null MEF cells with 1-chloro-2,4-dinitrobenzene (DNCB), a specific inhibitor of Trx reductase, provide evidence that STRAP Ser(188) phosphorylation plays a key role in STRAP-dependent cell death. Adenoviral delivery of MPK38 in mice also demonstrates that STRAP Ser(188) phosphorylation in the liver is tightly associated with cell death and proliferation through ASK1, TGF-β, p53, and PI3K/PDK1 pathways, resulting in apoptotic cell death.
- Chungbuk National University Korea (Republic of)
- Department of Biochemistry Switzerland
- Department of Biochemistry Hong Kong
Male, Pyruvate Dehydrogenase Acetyl-Transferring Kinase, RNA-Binding Proteins, Apoptosis, Protein Serine-Threonine Kinases, MAP Kinase Kinase Kinase 5, Cell Line, Mice, Inbred C57BL, Mice, Phosphatidylinositol 3-Kinases, HEK293 Cells, Transforming Growth Factor beta, Dinitrochlorobenzene, Serine, Animals, Humans, Phosphorylation, RNA, Small Interfering, Adaptor Proteins, Signal Transducing, Signal Transduction
Male, Pyruvate Dehydrogenase Acetyl-Transferring Kinase, RNA-Binding Proteins, Apoptosis, Protein Serine-Threonine Kinases, MAP Kinase Kinase Kinase 5, Cell Line, Mice, Inbred C57BL, Mice, Phosphatidylinositol 3-Kinases, HEK293 Cells, Transforming Growth Factor beta, Dinitrochlorobenzene, Serine, Animals, Humans, Phosphorylation, RNA, Small Interfering, Adaptor Proteins, Signal Transducing, Signal Transduction
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).23 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!