Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology

Supervisor(s)

Dr. John F. MacDonald

Abstract

TRPM2 is a calcium-permeable non-selective cation channel that acts as a mediator of cell death in response to oxidative stress. It has been shown that oxidative stress increases TRPM2 tyrosine phosphorylation and activation – an effect that is blocked by PP2, a non-specific inhibitor of Src family kinases. However, the kinase and target TRPM2 tyrosine residue(s) involved have not yet been identified. Here, we investigated the potential regulation of TRPM2 by Fyn. Intracellular application of recombinant Fyn potentiated TRPM2 currents in HEK293 cells expressing inducible TRPM2 (TRPM2-HEK293 cells). Further, a physical interaction between Fyn and TRPM2 was demonstrated by co-immunoprecipitation in TRPM2-HEK293 cells. Additionally, tyrosine phosphorylation of TRPM2 was induced by Fyn in TRPM2-HEK293 cells, and the amount of phosphorylation detected was related to the activation state of Fyn. We propose that by augmenting TRPM2 activity, Fyn kinase potentiates cellular calcium overload and facilitates cell death in response to oxidative stress.


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