Characterization of A-type ephrin signaling




Bazowski, Jessa

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Membrane attachment of ephrin ligands plays an important role in Eph receptor activation. Membrane anchorage is thought to provide a clustering effect to ephrins that is necessary for stimulation of Eph receptor kinase activity. The presence of soluble A-type ephrin in conditioned media of numerous cultured cancer cell lines and normal endothelial cells prompted me to question the purpose of ephrin release. In this thesis I show that ephrin A1, a potent angiogenic factor, is released from several cancer cell lines and is a substrate for tissue transglutaminase, a multifunctional enzyme with the ability to form covalent crosslinks between substrate proteins. I show that tissue transglutaminase crosslinking primes soluble ephrin A1 to promote Eph A2 activity. These results suggest a role for soluble A-type ephrins in promoting Eph receptor activity at distant sites and also indicate that ephrin A1 may be acting as a soluble angiogenic factor during tumor neovascularization.



ephrin, transglutaminase, Eph, oligomerization, clustering