Investigation of The Role of The Scaffold Protein Shc In Erk Signaling

<p>Cells respond to environmental changes by converting extracellular signals into intracellular events. Scaffolding proteins play important roles in generating specificity in intracellular signaling through the combinatorial use of protein domains and posttranslational modifications. Using the scaffold Shc (Src-homology collagen-like) as a model system, we explored novel mechanisms whereby this class of protein shapes signaling output. In the present work, we focused on the role of Shc in the MAP kinase Erk signaling both prior to and post-growth factor stimulation. Prior to growth factor stimulation, we found Erk to be a direct interacting partner of Shc. The two proteins associate through a non-canonical interface. This interaction blocks the phosphorylation of Erk and restricts its nuclear translocation. Post-growth factor stimulation, Erk is released from Shc through an allosteric mechanism facilitated by the binding between Shc and the activated growth factor receptor. Furthermore, fully activated Erk phosphorylates Shc on three threonine residues. These phosphorylated residues on Shc subsequently serve as platforms to mediate both a positive feedforward loop in prolonging Erk activity and crosstalk with Akt signaling through protein recruitment.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2015

Author dc:creator

• suen, kin man

Contributors dc:contributor

• JOHN E. LADBURY
• SWATHI ARUR
• CARMEN W. DESSAUER

• SIGNALING
• EGF RECEPTOR
• ERK
• MAPK
• AKT
• Biochemistry, Biophysics, and Structural Biology
• Medicine and Health Sciences

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/549

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1588