Sentences with word «ephrin»

Most of the peptides are antagonists, but the peptides targeting EphA2 are agonists that activate receptor signaling and endocytosis similarly to the natural ephrin ligands.

We have identified a number of peptides that bind to Eph receptors and inhibit ephrin binding by using phage display approaches.

Yeddula N, Xia Y Ke E, Beumer J, Verma IM (2015) Screening for Tumor Suppressors: Loss of ephrin receptor A2 cooperates with oncogenic KRAS in promoting lung adenocarcinoma.

These activities are independent of ephrin binding and / or kinase activity and their mechanism is not well understood but in some cases depends on Eph receptor phosphorylation on serine / threonine residues (red circle).

This leads to bidirectional signals emanating from Eph receptor - ephrin complexes positioned at sites of cell - cell contact.

This is unlike the natural ephrin ligands, each of which promiscuously binds to multiple Eph receptors.

The team was successful in getting the drug to piggyback on 123B9, an agent they devised to target an oncogene called EphA2 (ephrin type - A receptor 2).

Eph receptors on the exosomes were able to bind to ephrin molecules on the surface of growing neurons and repel the neuronal extensions.

This proves, for the first time, that cells can send ephrins and Ephs out to transmit signals over a distance.

«This is why it's so fundamentally important to understand how cells use this system to communicate,» says Rüdiger Klein, whose Department at the Max Planck Institute of Neurobiology is studying ephrins and Eph receptors.

They revealed that many of these exosomes contained ephrins and Ephs, and decoded the cellular mechanism by which they were packed into the exosomes.

However, Rüdiger Klein and his team at the Max Planck Institute of Neurobiology have now shown that cells can also pack and release active ephrins and Eph receptors through extracellular vesicles.

(h) Human phospho - receptor tyrosine kinase array for EphA2, EphB2 and EphB4 ephrin receptors from control BP (shCtr) and BP silenced for Tie2 (siTie2 I and siTie2 II).

In the 1990s, scientists found the first of those signaling systems, a family of ephrin proteins that are present in graded fashion in the brain and are involved in axon guidance.

Disrupting either the Wnt or ephrin pathway throws the growing axons off their targets, shifting the map from side to side.

The A-class ephrins are required for map formation along the anterior - posterior (front - to - back) axis and the B - class for medial - lateral (side - to - side) axis.

For intance, GluA2 binds to PDZ domains 4 and 5 (Dong et al 1997), while ephrin receptors bind to domains 6 and 7 (Torres et al 1998).

There is also evidence that some Eph receptors can increase cancer cell malignancy through non-canonical ephrin - independent and / or kinase - independent signaling activities (Figure 1B), which is the subject of ongoing work.

Studies by ours and other groups have shown that a number of EphA2 and EphA3 mutations inactivate Eph receptor canonical signaling by disrupting ephrin binding or kinase activity, consistent with a role of canonical signaling in tumor suppression.

Certain Eph receptors and ephrins promote tumor angiogenesis.

(B) An EphA4 peptide antagonist blocks ephrin - induced growth cone collapse in EphA4 - expressing axons, suggesting its usefulness for promoting neural repair.

For example, Eph receptors and ephrins take part in the formation of blood vessels, including the blood vessels that feed tumors, and regulate the malignant properties of cancer cells and their interplay with the tumor microenvironment.

This knowledge is useful for the development of disease treatments based on modulating Eph receptor / ephrin activities.

We have identified tyrosine and serine / threonine phosphorylation sites of Eph receptors and ephrins using mass spectrometry and investigated the signaling role of these phosphorylation sites.

Understanding the effects of Eph receptor mutations in cancer cells will help shed light on the role of the Eph receptor / ephrin system in cancer cell transformation, malignant progression and drug resistance.

More recently, we elucidated an additional mechanism of tumor suppression mediated by canonical ephrin - induced EphA2 signaling (Figure 1A), which leads to inhibition of the AKT - mTORC1 oncogenic pathway through interplay of EphA2 with a phosphatase that dephosphorylates the AKT serine / threonine kinase.

In addition, the ephrin - Eph system also plays a role in plastic processes, such as learning and regeneration, as well as in tumour growth and neurodegenerative diseases.

«This might mean that strategies to control exosome release could be used to interrupt the ephrin - Eph signaling pathway and thereby disrupt tumour growth,» he surmises.

Recently, however, ephrins and Eph receptors have also been found in extracellular vesicles / exosomes — small droplets of fat released by cells, used as transport vehicles, signal transmitters or for eliminating cell components.

Ephrins and Eph receptors have also been found in the exosomes of cancer cells.

Until recently, scientists assumed that ephrin / Eph signal transmission could only occur through direct cell - cell contact.

When an ephrin meets the Eph receptor of another cell, they join to form an ephrin - Eph complex.

One way this communication happens is through the ephrin / Eph - receptor system, which is able to guide cell migration and the growth of neuronal extensions.

Eph receptors and their binding partners, the ephrins, are found on the surface of almost all cell types.

It had always seemed clear that ephrins and Ephs could only trigger a signaling process by direct contact between two cells.

«This has thrown up the interesting question of what business Ephs and ephrins have in exosomes,» says Klein.

Eph receptors and their partner proteins, the ephrins, are vital for intercellular communication.

The ephrins and Eph receptors in angiogenesis.

Syk kinases are required for spinal commissural axon repulsion at the midline via the ephrin / Eph pathway.

Dufour A., Seibt J., Passante L., Depaepe V., Ciossek T., Frisén J., Kullander J., Flanagan J.G., Polleux F. and Vanderhaeghen P. (2003) Area - Specificity and topography of thalamocortical projections controlled by ephrin / Eph genes.

Binding to ephrin ligands on the surface of neighboring cells induces canonical signaling involving receptor clustering, autophosphorylation on tyrosine residues, and kinase activity - dependent downstream signaling.

We showed that the EphA2 receptor is upregulated in the tumor vasculature together with the ephrin - A1 ligand, which suggested a role in tumor angiogenesis that is now well established.

Signals through the ephrins can also be generated.

Collaborating groups have elucidated the structural features of several of these peptides in complex with the ligand - binding domain of Eph receptors, demonstrating that the peptides bind to the ephrin - binding pocket in the ligand - binding domain (Figure 3A).

(A) Eph receptor - ephrin binding at cell - cell contact sites results in the dimerization / clustering of Eph receptor - ephrin complexes, and initiation of canonical signals through the receptor cytoplasmic domain.