Phospho-EPHA2/EPHA5 (Y594) Antibody

Antibody Characteristics

The Phospho-EPHA2-Y594 antibody is a rabbit-derived polyclonal IgG antibody validated for Western blot (WB) and ELISA applications. Key specifications include:

Research Significance of EphA2-Y594 Phosphorylation

EphA2 is a receptor tyrosine kinase with dual roles: as a tumor suppressor in ligand-dependent signaling and an oncogene in ligand-independent contexts. Phosphorylation at Y594 is critical for its signaling dynamics:

• Oncogenic Signaling: Y594 phosphorylation promotes interactions with guanine nucleotide exchange factors (GEFs) like Vav2/3, driving Rac1/RhoA activation to enhance cell migration and invasion ( ).

• Proteolytic Regulation: In cancers, MT1-MMP-mediated EphA2 cleavage in tumor tissues correlates with increased Y594 phosphorylation, promoting ErbB signaling and metastasis ( ).

• Enzyme Targeting: Y594 is preferentially dephosphorylated by HCPTP-A/B phosphatases over adjacent residues (e.g., Y588), modulating downstream pathways ( ).

Cancer Relevance

• Tumor Microenvironment: In MT1-MMP-expressing tumors, Y594 phosphorylation is elevated in invasive regions, correlating with poor prognosis ( ).

• Therapeutic Targeting: Expression of a proteolysis-resistant EphA2 mutant (Y594F) suppresses tumor growth and metastasis in xenograft models ( ).

Applications in Research

• Mechanistic Studies: Used to investigate EphA2’s role in ligand-independent signaling, such as PI3K/Akt and RhoGEF-mediated pathways ( ).

• Biomarker Validation: Detects phosphorylated EphA2 in cell lines (e.g., SH-SY5Y, A431) and tumor tissues under conditions like serum starvation or ephrin-A1 stimulation ( ).

• Drug Development: Serves as a readout for inhibitors targeting EphA2 phosphorylation or proteolytic processing ( ).

Validation and Compatibility

• Specificity: Recognizes phosphorylated Y594 without cross-reactivity to non-phosphorylated EphA2 or other Eph receptors ( ).

• Model Systems: Validated in human and murine cell lines (e.g., HEK293, HeLa) and xenograft tissues ( ).

Limitations and Considerations

• Species Reactivity: Limited to human, rat, and mouse; unreactive with non-mammalian species ( ).

• Context-Dependent Signals: Phosphorylation levels vary with cellular conditions (e.g., serum starvation, ligand stimulation) ( ).