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Ephrin Ligands (ephrin + ligand)

Distribution by Scientific Domains
Chemistry75%

Selected Abstracts

Immunohistochemical profile of ephrin A4 expression in human osteosarcoma

APMIS, Issue 4 2009
ASMAA GABER ABDOU
Ephrin receptors and ephrin ligands constitute one of the largest groups of tyrosine kinases. The division of ephrin receptors into type A or type B is determined by their ligand-binding specificities. Ephrin A4 as a ligand has a broad capacity to bind and stimulate different subtypes of ephrin A receptors. Little is known about the role of ephrins generally and ephrin A4 particularly in osteosarcoma. Ephrin A4 was immunohistochemically assessed on archival material from 46 primary osteosarcoma cases, 10 metastatic pulmonary lesions and 20 normal control bone specimens. Ephrin A4 was expressed in 100% of normal bone specimens, in 84.4% of primary osteosarcoma cases and in all metastatic pulmonary lesions. Cytoplasmic and nucleocytoplasmic patterns of ephrin A4 immunoreactivity were observed, with the predominance of the latter pattern in normal bone (100%), and in 43.5% of primary osteosarcoma cases, which showed a higher intensity of expression compared with normal bone (p<0.05). The cytoplasmic pattern is the only staining pattern seen in metastatic cases, which may suggest its role in enhancement of invasion and metastasis. The differences in the distribution of the two patterns of ephrin A4 may indicate a different biological activity of this molecule depending on its localization. The nuclear localization of ephrin A4 requires further investigation to clarify the mechanism and the significance of the nuclear trafficking of ephrin A4. [source]

Purification, crystallization and preliminary characterization of an Eph-B2/ephrin-B2 complex

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2002
Juha-P.
Eph receptors and their ephrin ligands are involved in various aspects of cell,cell communication during development, including those of the axon pathfinding processes in the nervous system and cell,cell interactions of the vascular endothelial cells. The recognition and binding properties of the ligand-binding domain of EphB2 receptor and the extracellular domain of ephrin-B2 have been studied and two different cocrystals of their complex have been generated. One crystal form has space group C2, diffracts to 3.5,Å and has unit-cell parameters a = 128, b = 88, c = 79,Å, , = 112°. The other crystal form grows in space group P1, has unit-cell parameters a = 78, b = 78, c = 78,Å, , = 69, , = 75, , = 69° and diffracts to 2.7,Å. Structure-determination experiments using the latter form are in progress. The structure of the complex will elucidate the chemical nature of the interactions between Eph receptors and ephrins, which would create the possibility of using them as targets for structure-based anticancer-drug development. [source]

Structure of the ligand-binding domain of the EphB2 receptor at 2,Å resolution

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 2 2009
Yehuda Goldgur
Eph tyrosine kinase receptors, the largest group of receptor tyrosine kinases, and their ephrin ligands are important mediators of cell,cell communication regulating cell attachment, shape and mobility. Recently, several Eph receptors and ephrins have also been found to play important roles in the progression of cancer. Structural and biophysical studies have established detailed information on the binding and recognition of Eph receptors and ephrins. The initial high-affinity binding of Eph receptors to ephrin occurs through the penetration of an extended G,H loop of the ligand into a hydrophobic channel on the surface of the receptor. Consequently, the G,H loop-binding channel of Eph receptors is the main target in the search for Eph antagonists that could be used in the development of anticancer drugs and several peptides have been shown to specifically bind Eph receptors and compete with the cognate ephrin ligands. However, the molecular details of the conformational changes upon Eph/ephrin binding have remained speculative, since two of the loops were unstructured in the original model of the free EphB2 structure and their conformational changes upon ligand binding could consequently not be analyzed in detail. In this study, the X-ray structure of unbound EphB2 is reported at a considerably higher 2,Å resolution, the conformational changes that the important receptor loops undergo upon ligand binding are described and the consequences that these findings have for the development of Eph antagonists are discussed. [source]