Regulation of the golgi apparatus by p38 and JNK kinases during cellular stress responses

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

p38 and c-Jun N-terninal kinase (JNK) are activated in response to acute stress and inflammatory signals. Through modification of a plethora of substrates, these kinases profoundly re-shape cellular physiology for the optimal response to a harmful environment and/or an inflammatory state. Here, we utilized phospho-proteomics to identify several hundred substrates for both kinases. Our results indicate that the scale of signaling from p38 and JNK are of a similar magnitude. Among the many new targets, we highlight the regulation of the transcriptional regulators grb10-interacting GYF protein 1 and 2 (GIGYF1/2) by p38-dependent MAP kinase-activated protein kinase 2 (MK2) phosphorylation and 14–3–3 binding. We also show that the Golgi apparatus contains numerous substrates, and is a major target for regulation by p38 and JNK. When activated, these kinases mediate structural rearrangement of the Golgi apparatus, which positively affects protein flux through the secretory system. Our work expands on our knowledge about p38 and JNK signaling with important biological ramifications.

OriginalsprogEngelsk
Artikelnummer9595
TidsskriftInternational Journal of Molecular Sciences
Vol/bind22
Udgave nummer17
Antal sider23
ISSN1661-6596
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
The authors declare no competing financial interests. Work in the Bekker-Jensen lab was supported by grants from the Lundbeck Foundation (R190-2014-4037), The Danish Medical Research Council (9039-00007B), The NEYE Foundation, The Nordea Foundation, and the European Research Council (ERC) under the European Union?s Horizon 2020 research and innovation program (grant agreement 863911-PHYRIST). Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center, based at the University of Copenhagen, Denmark, and is partially funded by an unconditional donation from the Novo Nordisk Foundation (www.cbmr.ku.dk) (Grant number NNF18CC0034900). We thank Vivek Malhotra (Centro de Regulacion Genomica, Spain), Yan-zhuang Wang (University of Michigan, USA), Dong-Er Zhang (University of California San Diego, USA) and Roger Davis (University of Massachusetts, USA) for providing reagents. We also thank Luis Toledo (University of Copenhagen, Denmark) for help with high content microscopy and Fena Ochs (University of Copenhagen, Denmark) for help with Structured Illumination Microscopy. We acknowledge the Core Facility for Integrated Microscopy (University of Copenhagen, Den-mark) for providing access to super resolution microscopy. For providing access to confocal microscopy we acknowledge the Danstem and NNF-CPR imaging platform (University of Copenhagen, Denmark).

Funding Information:
Funding: The authors declare no competing financial interests. Work in the Bekker-Jensen lab was supported by grants from the Lundbeck Foundation (R190-2014-4037), The Danish Medical Research Council (9039-00007B), The NEYE Foundation, The Nordea Foundation, and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 863911-PHYRIST). Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center, based at the University of Copenhagen, Denmark, and is partially funded by an unconditional donation from the Novo Nordisk Foundation (www.cbmr.ku.dk) (Grant number NNF18CC0034900).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk


Ingen data tilgængelig

ID: 280064152