EphB2 and EphB3 forward signalling are required for palate development

The erythropoietin-producing hepatocellular carcinoma (Eph) receptor tyrosine kinase family plays important roles in developmental processes, adult tissue homeostasis, and various diseases. Interaction with Eph receptor-interacting protein (ephrin) ligands on the surface of neighboring cells triggers Eph receptor kinase-dependent signaling. The ephrins can also transmit signals, leading to bidirectional cell contact-dependent communication. Moreover, Eph receptors and ephrins can function independently of each other through interplay with other signaling systems. Given their involvement in many pathological conditions ranging from neurological disorders to cancer and viral infections, Eph receptors and ephrins are increasingly recognized as attractive therapeutic targets, and various strategies are being explored to modulate their expression and function. Eph receptor/ephrin upregulation in cancer cells, the angiogenic vasculature, and injured or diseased tissues also offer opportunities for Eph/ephrin-based targeted drug delivery and imaging. Thus, despite the challenges presented by the complex biology of the Eph receptor/ephrin system, exciting possibilities exist for therapies exploiting these molecules.

Ephrin

EPH receptor A2

Receptor Protein-Tyrosine Kinases

10.1146/annurev-pharmtox-011112-140226

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Citations (275)

Progress in The Reverse Signal Transduction Mediated by Eph-ephrin

PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS (2007)

Guoguang Zheng

Bidirectional signal transduction is a newly elucidated mechanism in intercellular communication. The bidirectional signal transduction mediated by the Eph-ephrin is an important representative in this field. The Eph family receptor tyrosine kinases and their membrane-bound ligands, the ephrins, play pivotal roles in the development of nervous system, angiogenesis, etc. The signal transduction into cells by Eph receptors is the forward signal, whereas the signal transduction by ephrins is the reverse signal. Based on their molecular structures, the ephrins can be divided into two subclasses, i.e. ephrinA and ephrinB. The ephrinBs are transmembrane proteins, which can activate FAK, JNK and Wnt signal transduction pathways through phosphotyrosine-dependent signaling and PDZ-binding motif-dependent signaling. The ephrinAs are glycosylphosphotidylinositol (GPI) anchored proteins, which can also mediate reverse signal transduction.

Ephrin

PDZ domain

Receptor Protein-Tyrosine Kinases

EPH receptor A2

Source

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Evaluation of the Anti-Tumor Activity of Small Molecules Targeting Eph/Ephrins in APC min/J Mice

Pharmaceuticals (2020)

Miriam Corrado Carmine Giorgio Elisabetta Barocelli Giuseppe Vittucci Marzetti Anna Maria Cantoni

The Eph receptors are the largest receptors tyrosine kinases (RTKs) family in humans and together with ephrin ligands constitute a complex cellular communication system often dysregulated in many tumors. The role of the Eph-ephrin system in colorectal cancer (CRC) has been investigated and different expression of Eph receptors have been associated with tumor development and progression. In light of this evidence, we investigated if a pharmacological approach aimed at inhibiting Eph/ephrin interaction through small molecules could prevent tumor growth in APC min/J mice. The 8-week treatment with the Eph-ephrin antagonist UniPR129 significantly reduced the number of adenomas in the ileum and decreased the diameter of adenomas in the same region. Overall our data suggested as UniPR129 could be able to slow down the tumor development in APC min/J mice. These results further confirm literature data about Eph kinases as a new valuable target in the intestinal cancer and for the first time showed the feasibility of the Eph-ephrin inhibition as a useful pharmacological approach against the intestinal tumorigenesis. In conclusion this work paves the way for further studies with Eph-ephrin inhibitors in order to confirm the Eph antagonism as innovative pharmacological approach with preventive benefit in the intestinal tumor development.

Ephrin

EPH receptor A2

Regorafenib

Receptor Protein-Tyrosine Kinases

10.3390/ph13040069

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Citations (1)

Mechanisms of ephrin–Eph signalling in development, physiology and disease

Nature Reviews Molecular Cell Biology (2016)

Artur Kania Rüdiger Klein

Ephrin

Signalling