Does Receptor Phosphorylation Affect Lateral Dimerization?

Abstract

Eph-A2 is a member of the largest Receptor Tyrosine Kinases (RTKs) family and hence it is activated through lateral dimerization. The dimerization of Eph-A2 receptor triggers signaling in the membrane plane that regulates many physiological processes in humans. This protein is very often overexpressed in a variety of cancers. EphA2 receptor is auto phosphorylated on Tyr through lateral dimerization and Serine phosphorylated by Akt. The Serine phosphorylation of EphA2 receptor is linked to tumorigenic behavior of EphA2 receptor. We asked if Serine phosphorylation and tyrosine phosphorylation can affect the dimerization of EphA2 receptor. We generated the kinase dead (K646M mutant) EphA2 and S897A EphA2 mutant. We studied the dimerization of these mutants using FRET based assay in live cells and compared with the wild type data. Out data suggest that both mutations affect dimerization.