Biomedical Sciences ETDs

Publication Date

Summer 7-31-2021

Abstract

Immunoreceptor Tyrosine-based Activating Motif (ITAM) receptors are critical in sensing extracellular antigen and initiating an immune response. The ITAM receptor FcɛRI, termed the high affinity IgE receptor, is the primary promoter of inducing the Type 1 allergic response and is primarily expressed in mast cells and basophils. In this dissertation, I worked to determine how early signaling events initiated at the FcɛRI ITAM interface tune downstream signaling outcomes. I began by determining that differential phospho-tyrosine ITAM patterns produce unique recruitment profiles of the accessory kinases proteins Syk and Lyn. I next determined the differential signaling ITAM capabilities of Lyn and Syk. This work revealed a novel signaling mechanism where Syk phosphorylates and binds the conserved FcɛRIγ ITAM dimer. Finally, I investigated how mechanical force and aggregate complexity may direct differential FcɛRI signaling profiles. These findings expand our understanding of how key signaling events contribute to tune the FcɛRI signaling cascade.

Keywords

Immune Signaling, ITAM, Mast Cell, Molecular Biology, Kinase, Fc Receptor

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Diane S. Lidke

Second Committee Member

Jennifer M. Gillette

Third Committee Member

Bryce Chackerian

Fourth Committee Member

Judy L. Cannon

Comments

This dissertation is currently placed under an embargo.

Download

Share

COinS