Disease relevance of EPHA4

• In normal chicks, the CEK4 and CEK8 eph-class receptor tyrosine kinases were expressed relatively heavily by the cochlear nerve ganglion, and CEK10 was expressed relatively heavily by the cochlear hair cell sensory epithelium [1].

High impact information on EPHA4

• These findings suggest that regional specification of motoneurons, at least of Cek8 and LNGFR expression, is independent of the notochord and the floor plate and that the whole neural tube appears to be committed to differentiate into the motoneuron subtypes along the A-P axis at the operative stages [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].
• Characterization of the expression of the Cek8 receptor-type tyrosine kinase during development and in tumor cell lines [3].
• Cek8 is expressed in nearly all of the tumor cell lines examined, including cell lines derived from tumors of the central nervous system [3].
• In the stage 24 chick embryo, Cek8 immunoreactivity is prominent in the spinal cord and spinal nerves [3].

Biological context of EPHA4

• The eph-class receptor tyrosine kinase CEK10 may be involved in cell interactions in the cochlear sensory epithelium, while CEK4 and CEK8 may play a role in the cochlear innervation [1].
• In situ hybridization revealed that Cek8, a member of the eph family, was specifically expressed on motoneurons at the brachial and lumbar segments of the spinal cord which innervate limb muscles, and disappeared after the naturally occurring cell death period (E6-E11) [4].
• Cross-linking of Cek8 molecules on the cell surface with wheat germ agglutinin caused their rapid phosphorylation on tyrosine [3].
• The 120 kd Cek8 protein is detected early in embryogenesis, is developmentally regulated and preferentially, but not exclusively, expressed in neural tissues [3].

Anatomical context of EPHA4

• The receptor tyrosine kinase, Cek8, is transiently expressed on subtypes of motoneurons in the spinal cord during development [4].
• Here we report the characterization of the Cek8 protein and its expression in embryonic tissues and tumor cell lines [3].
• At embryonic day 6, Cek8 expression becomes concentrated to the ventral portion of the spinal nerves, suggesting a role in axonogenesis of specific subsets of neurons [3].
• Although the phosphorylation on tyrosine of Cek8 during development is moderate or undetectable, Cek8 is substantially phosphorylated on tyrosine (and thus presumably activated) in many of the transformed cell lines [3].
• Both Cek5 and Cek8 are distributed in manners which are consistent with their regulating the outgrowth of retinal ganglion cell axons to the tectum [5].

Analytical, diagnostic and therapeutic context of EPHA4

• Immunohistochemistry using an anti-Cek8 monoclonal antibody showed the localization of Cek8 protein at the cell bodies and axonal fibers of motoneurons and muscles [4].

References