Disease relevance of EFNA2

• Methods: Female nude mice injected intraperitoneally with HeyA8 ovarian cancer cells were treated with either docetaxel alone or in combination with anti-angiogenic agents (AEE788-dual VEGFR and EGFR antagonist or EA5-monoclonal antibody against ephrin A2) [1].

High impact information on EFNA2

• Cleavage of ephrin-A2 by the ADAM10 membrane metalloprotease enables contact repulsion between Eph- and ephrin-expressing cells [2].
• We now show that activation of ephrin-A2 or ephrin-A5 by one of their receptors, ephA3, results in a beta 1-integrin-dependent increased adhesion of ephrin-A-expressing cells to laminin [3].
• Tyrosine phosphorylation of this protein is not seen after stimulating ephrin-A2-expressing cells with basic fibroblast growth factor, epidermal growth factor, insulin growth factor, or fetal calf serum containing a large set of different growth factors [3].
• A repulsive mechanism involving opposing gradients of the EphA3 receptor on retinal axons and its ligands, ephrin-A2 and ephrin-A5, in the tectum influences topographic mapping of the retinotectal projection [4].
• Recent reports have implicated Mek4, a member of the Eph (also named class V) family of tyrosine kinase receptors (RTKs), and two ligands, RAGS and ELF-1, in this process [5].

Biological context of EFNA2

• Using PCR-based screening of genomic DNA from human x rodent hybrid cell lines, the gene encoding ephrin-A2 (EFNA2) was assigned to chromosome 19 [6].
• Rac1-mediated endocytosis during ephrin-A2- and semaphorin 3A-induced growth cone collapse [7].

Anatomical context of EFNA2

• Unexpectedly, we found that many Eph receptors are expressed not only in retinal ganglion cells, but also in tectal cells, In particular, EphA3 mRNA is prominently expressed in the anterior tectum, with a pattern reciprocal to that of ephrin-A2 and ephrin-A5 [4].
• Here we show that optic nerve section in adult rat differentially regulates the expression of ephrin-A2 in the superior colliculus (SC) and of EphA5 in the retina [8].
• We confronted temporal retinal axons with precisely formed striped linear gradients of repellent tectal membranes and of two candidate repellent molecules, ephrin-A2 and -A5 [9].
• Furthermore, from stages 13-20 ephrin-A2 and ephrin-A5 ligands are only localized to the mesenchyme of the first branchial arch (maxillary and mandibular processes), the target fields for maxillomandibular trigeminal ganglion axons [10].
• Expression of EphA4, ephrin-A2 and ephrin-A5 during axon outgrowth to the hindlimb indicates potential roles in pathfinding [11].

Associations of EFNA2 with chemical compounds

• Ephrin-A5 and Ephrin-A2 are ligands for the EphA subfamily of Eph receptor tyrosine kinases, which are expressed in overlapping gradients in the posterior part of the tectum [12].

Other interactions of EFNA2

• While these results suggest that Ephrin-A5 and Ephrin-A2 form part of the posterior repulsive guidance activity, they do not elucidate whether they are necessary components [12].

Analytical, diagnostic and therapeutic context of EFNA2

• Expression was quantified immunohistochemically; ephrin-A2 levels were also estimated by semiquantitative reverse transcriptase polymerase chain reaction [8].
• We describe the expression of EphA3 and EphA7 receptors and ephrin-A2 ligand in the retina and the superior colliculus during the development of the retinocollicular projection in the marsupial wallaby (Macropus eugenii), using immunoblotting and immunohistochemistry [13].
• Double-labelling immunohistochemistry for ephrin-A2 and cell specific markers revealed that ephrin-A2 is expressed exclusively by a subset of neurons [14].
• Rac1 activity assays showed that Rac1 is transiently inactivated after treatment with ephrin-A2 [7].

References