Disease relevance of Epha1

• Eph-related receptor tyrosine kinases have been implicated in the control of axonal navigation and fasciculation [1].
• Here, we report that blocking Eph A class receptor activation inhibits angiogenesis in two independent tumor types, the RIP-Tag transgenic model of angiogenesis-dependent pancreatic islet cell carcinoma and the 4T1 model of metastatic mammary adenocarcinoma [2].
• To screen for Eph proteins expressed in tumor blood vessels, we used tumor xenografts grown in nude mice from MDA-MB-435 human breast cancer cells or KS1767 human Kaposi's sarcoma cells [3].
• The Eph family of receptor tyrosine kinases and their cell-presented ligands, the ephrins, are frequently overexpressed in a wide variety of cancers, including breast, small-cell lung and gastrointestinal cancers, melanomas, and neuroblastomas [4].
• Understanding the roles of Eph and ephrin in corneal angiogenesis may provide a therapeutic intervention for the treatment of angiogenesis-related disorders [5].

High impact information on Epha1

• Here we report that mural cells require ephrin-B2, a ligand for Eph receptor tyrosine kinases, for normal association with small-diameter blood vessels (microvessels) [6].
• The association of ephexin with Eph receptors constitutes a molecular link between Eph receptors and the actin cytoskeleton and provides a novel mechanism for achieving highly localized regulation of growth cone motility [7].
• We report the cloning and characterization of ephexin, a novel Eph receptor-interacting protein that is a member of the Dbl family of guanine nucleotide exchange factors (GEFs) for Rho GTPases [7].
• The Eph receptor tyrosine kinase family is regulated by autophosphorylation within the juxtamembrane region and the kinase activation segment [8].
• Eph receptors transduce short-range repulsive signals for axon guidance by modulating actin dynamics within growth cones [7].

Biological context of Epha1

• This study investigated the potential role of Eph-related molecules during very early embryonic development by examining their expression in embryonic stem (ES) cells and embryoid bodies differentiated from ES cells in vitro [9].
• In the latter, Eph receptors and their class-A (GPI-anchored) and class-B (transmembrane) ephrin ligands control cell migration and axon-pathfinding, help establish regional patterns and act as labels for cell positioning [10].
• These expression patterns define previously unknown developmental units and suggest that Eph family proteins may contribute to cerebellar morphogenesis [11].
• This loop, which is conserved within but not between Eph RTK subclasses, packs against the concave beta-sandwich surface near positions at which missense mutations cause signalling defects, localizing the ligand-binding region on the surface of the receptor [12].
• Tyrosine phosphorylation of transmembrane ligands for Eph receptors [13].

Anatomical context of Epha1

• However, one clone contained sequence from a novel Eph-subfamily member, which was termed embryonic stem-cell kinase or Esk [9].
• Several receptor tyrosine kinase genes of the Eph family are segmentally expressed in the developing hindbrain [14].
• Therefore, responses mediated through specific Eph family receptors (ELK and Eck) are discriminated by endothelial cells from different vascular bed sources [15].
• Bidirectional signals mediated by Eph receptor tyrosine kinases and their membrane-bound ligands, ephrins, play pivotal roles in the formation of neural networks by induction of both collapse and elongation of neurites [16].
• Binding of these ligands to Eph-related receptors did not, however, elicit measurable biological signals in cultured cells [17].

Associations of Epha1 with chemical compounds

• Characterization of the Epha1 receptor tyrosine kinase: expression in epithelial tissues [18].
• Biochemical analyses revealed that Ptpro dephosphorylates a phosphotyrosine residue conserved in the juxtamembrane region, which is required for the activation and signal transmission of Eph receptors [19].
• During the past year, Eph receptors have been shown to associate with glutamate receptors in excitatory neurons, suggesting a role in synapse formation or function [20].
• An Eph receptor regulates integrin activity through R-Ras [21].

Regulatory relationships of Epha1

• We conclude that specific members of the Eph/ephrin family are expressed in embryonic pancreas according to a dynamic temporal and regional pattern [10].
• We show that in the developing mouse cerebellar cortex, members of the Eph receptor gene family are expressed in mediolaterally alternating Purkinje cell segments [22].

Other interactions of Epha1

• Together with our previous finding that Sek (Sek-1) is expressed in r3 and r5 (Gilardi-Hebenstreit et al., 1992; Nieto et al., 1992), these data indicate that members of the Eph family of RTKs may co-operate in the segmental patterning of the hindbrain [14].
• Expression analysis of the Epha1 receptor tyrosine kinase and its high-affinity ligands Efna1 and Efna3 during early mouse development [23].
• In this study, we have isolated a full-length cDNA, encoding the mouse homologue of a previous partially characterized Eek protein, a member of Eph receptor tyrosine kinase family [24].
• Binding experiments on whole pancreas demonstrated the presence of functional Eph receptors [10].
• Juxtamembrane tyrosine residues couple the Eph family receptor EphB2/Nuk to specific SH2 domain proteins in neuronal cells [1].

Analytical, diagnostic and therapeutic context of Epha1

• Here we have identified the Eph and ephrin genes that are expressed in mouse embryonic pancreas, as detected by RT-PCR analysis [10].
• Immunohistochemistry demonstrated that the expression of Eph A1 on endometrial epithelial cells and ephrin A1 and A3 expression on embryos decreased at implantation sites [25].
• The Eph family of receptor tyrosine kinases has been implicated in many developmental patterning processes, including cell segregation, cell migration, and axon guidance [26].
• To examine the potential scope of action for these genes in the nervous system, we have used in situ hybridization to study the mRNA expression of ephrins (B1, B2, and B3) and Eph receptors (B1, B2, B3, A4) in neonatal and adult mice [27].
• Abnormal topographic maps are reported in a knock-in experiment with elevated density of Eph receptors and a knock-out experiment lacking ephrin ligands using gene-targeting technology [28].

References