Graduation Year
2019
Graduation Month
May
Document Type
Thesis
Degree Name
Bachelor of Science
School or Department
Biological Sciences, Division of
Major
Biology – Cellular and Molecular Biology
Faculty Mentor Department
Biological Sciences, Division of
Faculty Mentor
Mark Grimes
Keywords
PAG1, Src-family kinases, neuroblastoma, cell signaling, exosomes
Subject Categories
Cancer Biology | Cell Biology | Developmental Biology | Other Cell and Developmental Biology
Abstract
The receptor tyrosine kinases (RTKs) are known to help regulate cell behaviors including differentiation, proliferation and migration during embryonic development of the neural crest. RTKs are believed to initiate signaling cascades in response to extracellular cues in part by controlling localization of Src-family kinases (SFKs). The scaffolding protein PAG1 binds SFKs and is believed to influence SFK activity and location within the cell by promoting interaction of SFKs with regulatory proteins and by drawing SFKs into different components of the endocytic pathway. By targeting the PAG1 gene in SH-SY5Y neuroblastoma cells with CRISPR/Cas9 plasmids, we created PAG1-mutant cell-lines in which a truncated, cytosolic form of PAG1 is expressed. Here I show that PAG1 mutants display increased proliferation. Furthermore I show that proliferation in PAG1 mutants was less sensitive to SFK inhibition than proliferation in wild-type cells. This was surprising because previously collected data had demonstrated that PAG1 mutants have higher levels of actively phosphorylated SFKs (pSFKs). SFKs may be increasingly targeted to multivesicular endosomes (MVEs) in PAG1 mutants, which can fuse with the plasma membrane releasing exosomes. Normally, SH-SY5Y cells release exosomes containing SFKs including LYN and FYN. Here, I show that exosomes released from PAG1 mutants contain lower levels of LYN and pSFKs than those from wild-type cells.
Honors College Research Project
Yes
GLI Capstone Project
no
Recommended Citation
Mayfield, Makenzie E., "Effects of PAG1 on Src-family kinase trafficking in neuroblastoma cells" (2019). Undergraduate Theses, Professional Papers, and Capstone Artifacts. 238.
https://scholarworks.umt.edu/utpp/238
Included in
Cancer Biology Commons, Cell Biology Commons, Developmental Biology Commons, Other Cell and Developmental Biology Commons
© Copyright 2019 Makenzie E. Mayfield