Date of Award
Spring 4-24-2022
Document Type
Thesis
Publication Status
Version of Record
Degree Name
Master of Science (MS)
Department
Biological Sciences
First Advisor
Joseph Kissil
Second Advisor
Catherine Trivigno
Abstract
The p21-activated kinase 1 (PAK1) is a member of the PAK protein kinase family that plays a role in cell proliferation, motility, and survival. Dysregulation of PAK1 stimulates growth of cancer cells. Currently identified PAK1 inhibitors present challenges related to efficacy, toxicity, and selectivity of the inhibitors. To overcome these issues, we are developing a novel cell-based assay, utilizing a kinase translocation reporter (KTR) approach to identify PAK1-specific inhibitors that are potent and exhibit limited toxicity. This assay tracks the nucleocytoplasmic shuttling of a PAK1-substrate-green fluorescent (GFP) fusion protein. Cellular localization of GFP can ascertain the level of PAK1 activity. Investigation into whether PAK1 mediated phosphorylation results in translocation of the reporter from the nucleus and whether additional modifications to the KTR reporter are necessary is ongoing. Development of this assay will allow generation of stable cell lines that express the KTR reporter to identify PAK1 inhibitors via high-throughput screening.
Recommended Citation
Harbaugh, David, "DEVELOPMENT OF A KINASE TRANSLOCATION REPORTER FOR HIGH-THROUGHPUT SCREENING OF NOVEL PAK1 INHIBITORS" (2022). Honors Theses. 3.
https://digitalcommons.fau.edu/honors_theses/3