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New genetically‐encodable tools to probe the nuanced regulation of the Extracellular signal‐regulated kinase (ERK) pathway
Author(s) -
Keyes Jeremiah,
Romania Taylor,
Boaks Adam,
Kotau Aliaksandr,
Baldwin Peter,
Slye Kevin
Publication year - 2022
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.2022.36.s1.l8010
Subject(s) - mapk/erk pathway , microbiology and biotechnology , kinase , biology , signal transduction , extracellular , protein kinase a
The Extracellular signal‐regulated kinase (ERK) signaling axis is activated by a host of divergent signaling molecules which each induce their own specific responses. These cellular responses include fundamental processes such as proliferation, differentiation, migration, and, under certain conditions, even apoptosis. Thus, the ubiquitous utilization of ERK signaling in variable and contrasting cellular processes makes it difficult to inhibit the pathway without causing adverse side effects. Furthermore, dysregulation of the Ras/Raf/MEK/ERK signaling pathway is directly implicated in a variety of disorders ranging from cancer to diabetes. Here, we report new tools to elucidate the nuanced mechanisms of differential regulation of the ERK pathway. First, we report a new genetically‐encodable tool to inhibit ERK at specific subcellular locations, allowing us to explore the specific function and mechanisms of regulation of ERK with extremely precise subcellular resolution. Additionally, we report a new genetically‐encodable fluorescent biosensor based on previous generations of the ERK‐kinase activity reporter (EKAR). Our new biosensor, which we have termed reDox‐EKAR1, allows us to probe into the spatiotemporal activity of ERK towards a different class of substrates than substrates probed by previous generations of EKAR. Utilizing these new tools, we report how specific pools of ERK regulate particular cellular functions previously underappreciated in the field, and we present our preliminary results detailing how these specific subcellular pools of ERK are differentially regulated.