The Eph family of receptor tyrosine kinases and their Ephrin ligands are important for cell positioning and morphogenesis during development. Eph receptors are classified into 10 EphA and 6 EphB receptors, which preferentially bind to the type A and type B ephrins, respectively. Ephrin type-A receptor 2 (EphA2), also known as epithelial cell kinase (Eck), binds the ephrin A1 (EFNA1) ligand, and has roles in neuronal development and repair, as well as carcinogenesis. EphA2 receptor has an N-terminal ligand-binding domain followed by a cysteine-rich domain with an epidermal growth factor-like motif and two fibronectin type-III repeats in the extracellular region, and a sterile alpha motif (SAM), and a PDZ domain-binding motif in the intracellular region. EphA2 is expressed in many types of cancers, including breast, colon, bladder, gastric, and glioblastoma. In bladder cancers, EphA2 may be activated by progranulin leading to phosphorylation at Ser-897 and bladder tumorigenesis. EphA2 may be an important therapeutic target and biomarker for several types of cancer.
