Eph kinases constitute the largest group of transmembrane receptor tyrosine kinases. Along with their ephrin ligands, these Eph kinases have been extensively studied for their roles in embryonic development and the central nervous system. EphA2 also plays a role in tumorigenesis, and until recently its exact role in tumor etiology and progression has been highly controversial as EphA2 demonstrates both pro- and anti-oncogenic properties.
EphA2 is a powerful oncoprotein, as it confers malignant potential on nontransformed epithelial cells.1 Furthermore, overexpression of EphA2 is consistently associated with disease progression and highly malignant cellular phenotypes including metastasis.2
On the other hand, EphA2 displays tumor suppressor characteristics. Binding of EphA2 to its ligand ephrin A1 has been shown to inhibit integrin signaling, the Ras/ERK pathway, and Rac GTPase activation, which all correlate with cell proliferation and migration inhibition.3 Moreover, EphA2 has been shown to play an important role in the p53-mediated cell apoptosis pathway. Finally, in EphA2 knock-out mice, inactivation of EphA2 resulted in increased susceptibility to skin carcinogenesis.4
The apparent contradictory roles of EphA2 in tumorigenesis were recently resolved by Dr. Bingcheng Wang's lab. EphA2 Ser897 phosphorylation was found to promote tumor cell migration and invasion. In human astrocytoma, Ser897 phosphorylation correlated with higher tumor grades.5 Activation of EphA2 with its ligand ephrin-A1 inhibited Ser897 phosphorylation, thereby leading to reduced chemotactic migration of glioma and prostate cancer cells.5 Thus, ligand-independent EphA2 Ser897 phosphorylation proved to be the oncogenic switch. This notion was further supported by recent work from Dr. Jennifer Issacs' lab. Extracellular molecular chaperone Hsp90 (eHsp90) was found to confer glioblastoma multiforme (GBM) cell motility and invasion, also through AKT mediated phosphorylation of EphA2 (Ser897).6
By using our unique NatureTope™ Technology*, Cell Applications, Inc. has been able to develop a novel Phospho-Ser897 EphA2 rabbit antibody which is now available to researchers. As shown in the Western Blot figure, this antibody specifically reacts with phosphorylated Serine 897 EphA2 in primary human astrocytes stimulated with fetal bovine serum. It also detects phosphorylated Ser897 EphA2 molecules in paraffin-embedded human ovarian cancer tissue. This novel Phospho-EphA2 (Ser897) antibody (Cat# CY1108) may prove to be a powerful tool to explore the important functions of EphA2.
