STRUCTURAL AND FUNCTIONAL STUDIES OF THE EFFECTS OF PHOSPHORYLATION ON EPHRIN RECEPTOR TYROSINE KINASE, EPHA2

STRUCTURAL AND FUNCTIONAL STUDIES OF THE EFFECTS OF PHOSPHORYLATION ON EPHRIN RECEPTOR TYROSINE KINASE, EPHA2

Bibliographic Details
Main Author: Javier, Fatima Raezelle Santos
Language:English
Published: Case Western Reserve University School of Graduate Studies / OhioLINK 2018
Subjects:
Biophysics
Physiology
receptor-tyrosine kinase
intracellular domains
EphA2 receptor
protein-protein interactions
protein-lipid interactions
microscale thermophoresis
kinase activity assays
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=case1523027075371687
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-case15230270753716872021-08-03T07:05:53Z STRUCTURAL AND FUNCTIONAL STUDIES OF THE EFFECTS OF PHOSPHORYLATION ON EPHRIN RECEPTOR TYROSINE KINASE, EPHA2 Javier, Fatima Raezelle Santos Biophysics Physiology receptor-tyrosine kinase intracellular domains EphA2 receptor protein-protein interactions protein-lipid interactions microscale thermophoresis kinase activity assays Erythropoietin-producing human hepatocellular (Eph) receptors account for the majority of the membrane-bound receptor tyrosine kinase (RTK) family. Eph receptors have significant roles during embryonic development, cell maturation, and adulthood. Furthermore, studies have shown that drastic increase in the expression of Eph receptors is detected in the malignant proliferation of tumor cells in numerous cancers, such as melanoma, breast cancer and glioblastoma. Indeed, recently, oncogenic activities have been observed in non-canonical unliganded Ephrin type-A receptor 2 (EphA2). This project aims to probe the effects of phosphorylation on the intracellular domain interactions of EphA2 in solution. Results from this study indicate that deletion of the sterile a motif (SAM) domain leads to a strong binding affinity between kinase domains in solution. Upon oligomerization, less kinase activity is observed, compared to that of the monomeric state of the intracellular domain (ICD) of EphA2. Moreover, in this study, microscale thermophoresis (MST) is utilized to assess the binding interactions of EphA2 in complex with liposomes, a membrane-like environment. Upon the truncation of the SAM domain, binding of the intracellular domains of EphA2 to the membrane is abrogated. Data from this study will help to elucidate and further our understanding of the signaling mechanism of receptor tyrosine kinases and the regulatory role of phosphorylation. 2018-06-01 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1523027075371687 http://rave.ohiolink.edu/etdc/view?acc_num=case1523027075371687 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Biophysics
Physiology
receptor-tyrosine kinase
intracellular domains
EphA2 receptor
protein-protein interactions
protein-lipid interactions
microscale thermophoresis
kinase activity assays
spellingShingle Biophysics
Physiology
receptor-tyrosine kinase
intracellular domains
EphA2 receptor
protein-protein interactions
protein-lipid interactions
microscale thermophoresis
kinase activity assays
Javier, Fatima Raezelle Santos
STRUCTURAL AND FUNCTIONAL STUDIES OF THE EFFECTS OF PHOSPHORYLATION ON EPHRIN RECEPTOR TYROSINE KINASE, EPHA2
author Javier, Fatima Raezelle Santos
author_facet Javier, Fatima Raezelle Santos
author_sort Javier, Fatima Raezelle Santos
title STRUCTURAL AND FUNCTIONAL STUDIES OF THE EFFECTS OF PHOSPHORYLATION ON EPHRIN RECEPTOR TYROSINE KINASE, EPHA2
title_short STRUCTURAL AND FUNCTIONAL STUDIES OF THE EFFECTS OF PHOSPHORYLATION ON EPHRIN RECEPTOR TYROSINE KINASE, EPHA2
title_full STRUCTURAL AND FUNCTIONAL STUDIES OF THE EFFECTS OF PHOSPHORYLATION ON EPHRIN RECEPTOR TYROSINE KINASE, EPHA2
title_fullStr STRUCTURAL AND FUNCTIONAL STUDIES OF THE EFFECTS OF PHOSPHORYLATION ON EPHRIN RECEPTOR TYROSINE KINASE, EPHA2
title_full_unstemmed STRUCTURAL AND FUNCTIONAL STUDIES OF THE EFFECTS OF PHOSPHORYLATION ON EPHRIN RECEPTOR TYROSINE KINASE, EPHA2
title_sort structural and functional studies of the effects of phosphorylation on ephrin receptor tyrosine kinase, epha2
publisher Case Western Reserve University School of Graduate Studies / OhioLINK
publishDate 2018
url http://rave.ohiolink.edu/etdc/view?acc_num=case1523027075371687
work_keys_str_mv AT javierfatimaraezellesantos structuralandfunctionalstudiesoftheeffectsofphosphorylationonephrinreceptortyrosinekinaseepha2
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