Eph receptor

Eph Receptor

The Eph receptors are a group of receptor tyrosine kinases that are crucial for various developmental processes, particularly in the nervous system. They are the largest subfamily of receptor tyrosine kinases and are involved in mediating cell-cell communication.

Structure

Eph receptors are characterized by a conserved structure that includes an extracellular region, a single transmembrane segment, and a cytoplasmic tyrosine kinase domain. The extracellular region typically contains a ligand-binding domain, a cysteine-rich region, and two fibronectin type III repeats.

Classification

Eph receptors are divided into two classes based on their sequence homology and ligand-binding preferences:

• EphA receptors: These receptors generally bind to ephrin-A ligands, which are tethered to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor.
• EphB receptors: These receptors typically interact with ephrin-B ligands, which are attached to the cell membrane through a transmembrane domain.

Function

Eph receptors play a pivotal role in:

• Axon guidance: They help in the navigation of axons to their appropriate targets during neural development.
• Tissue boundary formation: Eph-ephrin interactions are crucial in establishing and maintaining boundaries between different cell populations.
• Angiogenesis: They are involved in the formation of new blood vessels.
• Cell migration and adhesion: Eph receptors regulate cell movement and adhesion, influencing processes such as cancer metastasis.

Signaling

Eph receptor signaling is bidirectional, meaning that both the receptor-expressing cell and the ligand-expressing cell can transduce signals. This is known as forward and reverse signaling:

• Forward signaling: Initiated by the binding of ephrin ligands to Eph receptors, leading to receptor clustering and autophosphorylation, which activates downstream signaling pathways.
• Reverse signaling: Occurs when the ephrin ligand transduces a signal into the ligand-expressing cell upon binding to an Eph receptor.

Clinical Significance

Eph receptors have been implicated in various diseases, including:

• Cancer: Aberrant Eph receptor signaling is associated with tumor growth, angiogenesis, and metastasis.
• Neurodegenerative diseases: Altered Eph-ephrin signaling is linked to conditions such as Alzheimer's disease.

Research and Therapeutic Potential

Due to their involvement in critical developmental and pathological processes, Eph receptors are considered potential targets for therapeutic intervention. Research is ongoing to develop drugs that can modulate Eph receptor activity for treating cancer and other diseases.

See Also

• Receptor tyrosine kinase
• Cell signaling
• Axon guidance

References

• Pasquale, E. B. (2005). Eph receptor signalling casts a wide net on cell behaviour. Nature Reviews Molecular Cell Biology, 6(6), 462-475.
• Kullander, K., & Klein, R. (2002). Mechanisms and functions of Eph and ephrin signalling. Nature Reviews Molecular Cell Biology, 3(7), 475-486.