RENEWED SIGNIFICANCE OF RAS GTPASES

Author

Michael Wey

Graduation Semester and Year

2017

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry

Department

Chemistry and Biochemistry

First Advisor

Jongyun Heo

Abstract

The Ras superfamily of GTPases act as molecular switches and play a critical role in intracellular signal transduction. These GTPases cycle between an active GTP- bound form and an inactive GDP-bound form to regulate a myriad of cellular processes. However, this classical model of Ras regulation does not accurately project the entire picture of Ras regulation. This work discusses non-classical and newly discovered elements of the Ras signaling network. While intrinsic kinetic properties of Ras are included in the classical model of Ras regulation, the importance of them is understated. We show that the development Costello Syndrome from somatic Harvey Ras (HRas) mutations, are due to the altered intrinsic kinetic properties of HRas by the mutation. This is counter to the belief, which many believe, that the intrinsic kinetic properties of Ras do not contribute significantly to the overall regulation of Ras. Recently, the discovery of Embryonic Ras (ERas) has given the Ras subfamily a new and atypical member. While ERas shares significant homology to the other Ras proteins, it has its own unique characteristics such as an extended N-terminus and unusual residues in its G domain. These ERas specific-unusual G domain residues make ERas constitutively active. While not naturally expressed in humans, ERas is found to be expressed in certain human cancers. There have been conflicting reports on the ERas-mediated cell-signaling pathways. My research, equipped with kinetic binding approaches, aims to characterize the ERas-binding interactions with key Ras-effector proteins that delineates the ERas-specific cell-signaling cascades.

Keywords

Ras, GTPase, Enzyme kinetics

Disciplines

Chemistry | Physical Sciences and Mathematics

License

This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.

Comments

Degree granted by The University of Texas at Arlington

Recommended Citation

Wey, Michael, "RENEWED SIGNIFICANCE OF RAS GTPASES" (2017). Chemistry & Biochemistry Dissertations. 203.
https://mavmatrix.uta.edu/chemistry_dissertations/203