Disease relevance of EPHB2

• The report that a receptor of the EphB subfamily, EphB2/Cek5/Nuk/Sek3, is expressed in a high ventral to low dorsal gradient in the developing chick retina and is present on ganglion cell axons suggests that it may be involved in the mapping of retinal axons along the corresponding dorsal-ventral axis of the tectum [1].

High impact information on EPHB2

• Cek5, a membrane receptor-type tyrosine kinase, is in neurons of the embryonic and postnatal avian brain [2].
• Cek5 is a recently identified receptor-type tyrosine kinase of the Eph subclass that is nearly ubiquitously expressed during embryonic development (Pasquale, 1991) [2].
• By means of immunofluorescence microscopy and high-resolution immunoelectron microscopy, Cek5 was found to be expressed in many regions of the chicken brain at various developmental stages, most notably in the hippocampus and cerebellum [2].
• However, as we show, Cek8 is not unique among the Eph-related kinases: another member of the Eph subclass, Cek5, has similar patterns of expression and phosphorylation in tumor cells [3].
• Variants of Cek10 and of Cek5 (a previously identified Eph-related kinase) containing amino acid insertion sequences in the juxtamembrane domain were also isolated [4].

Biological context of EPHB2

• Its wide tissue distribution throughout development and its sustained expression in adult brain suggest that Cek5 is an important component of signal transduction pathways, likely to interact with a widely distributed and important ligand, which is as yet unknown [5].
• The expression of Cek5 in the brain gradually diminishes during embryonic development, whereas in the skeletal muscle of the thigh a sharp decrease in Cek5 expression was detected at the time of terminal muscle differentiation [5].
• Additional transient transfection with Cek5 cDNA led to expression of Cek5 in its tyrosine-phosphorylated, activated form [6].
• This gene structure is similar to the structure of the chick EphB2 (Cek5) gene, except for one intron present between the first two exons encoding the EphA8 kinase domain [7].

Anatomical context of EPHB2

• The Cek5 variant is expressed in the brain, but not in other tissues of the 10-day chick embryo [4].
• Both Cek5 and Cek8 are distributed in manners which are consistent with their regulating the outgrowth of retinal ganglion cell axons to the tectum [8].
• Cek5 immunoreactivity is highly concentrated in only a portion of the optic nerve and optic chiasm, and in retinal cultures, Cek5 is detected in neurons [8].

Associations of EPHB2 with chemical compounds

• Chicken embryo kinase 5 (Cek5) is a transmembrane tyrosine kinase of the Eph family that was identified by screening a 10-d chicken embryo cDNA expression library with anti-phosphotyrosine antibodies [5].

Other interactions of EPHB2

• The extracellular region of Cek5 contains a cysteine rich N-terminal subdomain and a C-terminal subdomain mostly devoid of cysteines and comprising two repeats similar to fibronectin type III repeats [5].

Analytical, diagnostic and therapeutic context of EPHB2

• Immunoblotting experiments with anti-Cek5 polyclonal antibodies indicated that Cek5 is a membrane-associated 120-kDa protein containing intramolecular (but not intermolecular) disulfide bonds [5].
• RT-PCR established that the differential regulation of Cek5 expression in different portions of the retina occurs at the transcriptional level [8].

References