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

Javier, Fatima Raezelle Santos

Abstract Details

2018, Master of Sciences, Case Western Reserve University, Physiology and Biophysics.
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.
Matthias Buck (Advisor)
Sudha Chakrapani (Committee Member)
Rajesh Ramachandran (Committee Member)
Bingcheng Wang (Committee Member)
William Schilling (Committee Chair)
74 p.

Recommended Citations

Citations

  • Javier, F. R. S. (2018). STRUCTURAL AND FUNCTIONAL STUDIES OF THE EFFECTS OF PHOSPHORYLATION ON EPHRIN RECEPTOR TYROSINE KINASE, EPHA2 [Master's thesis, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1523027075371687

    APA Style (7th edition)

  • Javier, Fatima Raezelle. STRUCTURAL AND FUNCTIONAL STUDIES OF THE EFFECTS OF PHOSPHORYLATION ON EPHRIN RECEPTOR TYROSINE KINASE, EPHA2. 2018. Case Western Reserve University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1523027075371687.

    MLA Style (8th edition)

  • Javier, Fatima Raezelle. "STRUCTURAL AND FUNCTIONAL STUDIES OF THE EFFECTS OF PHOSPHORYLATION ON EPHRIN RECEPTOR TYROSINE KINASE, EPHA2." Master's thesis, Case Western Reserve University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1523027075371687

    Chicago Manual of Style (17th edition)