Date of Award


Degree Type


Degree Name

Master of Science




Dr. Susan Meakin

Second Advisor

Dr. David Litchfield

Third Advisor

Dr. Sean Cregan


The Fibroblast Growth Factor Receptor Substrate (Frs) family of lipid-anchored adapter proteins consists of Frs2 and Frs3, which are expressed in the developing nervous system. In the presence of Fibroblast Growth Factor (FGF) or Nerve Growth Factor (NGF), Frs2 and Frs3 can associate with the receptor tyrosine kinases TrkA and FGFR1, become tyrosine phosphorylated, and recruit Grb2 and Shp2, known mediators of FGF and neurotrophin signaling. For Frs2, this can lead to the downstream activation of the Erk and PI-3K signaling pathways; for Frs3, however, the consequences of these signaling events are unclear. To begin investigating the role of Frs3 in neuronal cells, we created a stable, undifferentiated PC12 cell line (Clone 23) permitting inducible Frs3 expression. While culturing these cells, we noticed that serum-deprived Frs3-expressing Clone 23 PC12 cells survive longer than their non-Frs3-expressing counterparts. Since PC12 serum deprivation is a classical model for studying apoptosis, we investigated whether Frs3 promotes survival in Clone 23 PC12 cells by inhibiting serum deprivation- induced apoptosis. Together, results from MTT, Hoechst, and immunoblotting assays suggest that Frs3 can delay serum deprivation-induced mitochondrial apoptosis in Clone 23 PC12 cells by promoting cell cycle progression.



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