(664.31) New genetically-encodable tools to probe the nuanced regulation of the Extracellular signal-regulated kinase (ERK) pathway

Poster Board Number: A298

Jeremiah Keyes (Penn State University Erie, Penn State University Erie), Taylor Romania (Penn State University Erie), Adam Boaks (Penn State University Erie), Aliaksandr Kotau (Penn State University Erie), Peter Baldwin (Penn State University Erie), Kevin Slye (Penn State University Erie)

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.

Support or Funding Information

Pennsylvania State University

Magee Womens Research Institute - Pennsylvania State University Erie Seed Grant

lt;pgt;Pennsylvania State University
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