The EPH and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases. They have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the Eph subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ligands for Eph receptors have been named ephrins by the Eph Nomenclature Committee (1997). Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. The Eph Nomenclature Committee (1997) proposed that Eph receptors interacting preferentially with ephrin-A proteins be called EphA and Eph receptors interacting preferentially with ephrin-B proteins be called EphB. By screening a HeLa cell cDNA library with degenerate oligonucleotides based on highly conserved regions of receptor protein-tyrosine kinases, Lindberg and Hunter (1990) isolated cDNAs encoding EPHA2, named ECK by them. The predicted 976-amino acid protein consists of a 534-amino acid external domain that includes a signal peptide; a 24-amino acid transmembrane domain; and a 418-amino acid cytoplasmic domain that contains a canonical protein-tyrosine kinase catalytic domain. Immunoprecipitated ECK from human cells migrated as an approximately 125- to 130-kD doublet by SDS-PAGE.
NCBI Summary:
This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene encodes a protein that binds ephrin-A ligands.
General function
Receptor
Comment
To identify receptor tyrosine kinases (RTKs) present in the murine inner ear, a degenerate polymerase chain reaction (PCR) methodology was employed to clone partial cDNAs encoding RTKs from embryonic day-17.5 mouse whole inner ear RNA. At least 20 distinct TKs were identified within the first 50 subcloned PCR products obtained by this analysis. One of the receptor RTKs identified encoded an eph-related kinase not previously described in the mouse. Analysis of full-length cDNAs revealed that this RTK is the mouse homolog of the rat ehk-2 gene product (Maisonpierre et al., 1993).
Cellular localization
Plasma membrane
Comment
Ovarian function
Comment
Expression regulated by
Comment
Ovarian localization
Granulosa
Comment
Northern blot analysis detected an approximately 4.7-kb ECK transcript in human cells. Rat EphA2 mRNA is highly expressed in tissues that contain a high proportion of epithelial cells, including lung, skin, small intestine, and ovary (Lindberg et al 1990).Expression of Eph Receptor Tyrosine Kinases and their Ligands in Human Granulosa Lutein Cells and Human Umbilical Vein Endothelial Cells. Xu Y et al. Corpus luteum development is regulated by gonadotropins and accompanied by extremely rapid vascularization of the avascular granulosa cell compartiment by endothelial cells (EC). The proliferation of Granulosa cells (GC) and EC is a complex interplay and takes place in a spatially and temporarily coordinated manner. The erythropoietin-producing hepatoma amplified sequence (Eph) receptors and their ligands-the ephrins- are a recently detected family of membrane located protein tyrosine kinases which play a crucial role in the growth and development of nerve and blood vessel network. We report about the mRNA expression pattern of Ephs and their ligands in human GC, in human EC, and in carcinoma cell lines OvCar-3 and Hela. The mRNA of EphA4, EphA7, ephrinA4, ephrinB1 and ephrinB2 was detected in GC and EC, while EphA2 was expressed only in GC. The expression of various Ephs and ephrins did not change in GC after stimulation with human chorion gonadotropin. Our study analyzes for the first time the expression of the complete human Eph/ephriny-system in GC and in EC. The remarkable similarity between these two cell types supports the theory of a functional relationship of EC and GC. In addition, it was shown that hCG is not a major determinant of Eph/ephrin regulation in GC.
Follicle stages
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment:Chen J, et al reported that germ-line inactivation of the murine Eck receptor tyrosine
kinase by gene trap retroviral insertion.
The study characterized a mutation in the Eck receptor tyrosine kinase
gene induced by the U3betageo gene trap retrovirus. The provirus inserted approximately 8 kb upstream of the
5' end of the published cDNA sequence, and 1.8 kb downstream of an
alternatively spliced 5' exon. The eck(i) allele is essentially a null mutation since
mutant mice are severely deficient for Eck protein as determined by Western blot
analysis and in vitro kinase assays. Nevertheless, mice homozygous for the
mutation did not exhibit any discernable phenotype. These results suggest that
other members of the Eph family of receptor tyrosine kinases can functionally
compensate for loss of Eck.