Hepatoma transmembrane kinase (EPHB4; OMIM 600011) is a member of the Eph receptor family. It has a wide tissue distribution,
including expression in several myeloid hematopoietic cell lines. Bennett et al. (1995) sought to define the functional role of HTK by
cloning its cognate ligand from a kidney cell line. Both human and mouse EPLG5 clones were ultimately obtained.
They found that the ligand cDNA encodes a transmembrane protein of 336 amino acids. Incubation of 3T3 cells
expressing HTK with COS-7 cells expressing the ligand resulted in tyrosine phosphorylation of HTK. The ligand, like
its receptor, is widely expressed and may function in a variety of tissues.
NCBI Summary:
This gene encodes a member of the ephrin (EPH) family. The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, especially in the nervous system and in erythropoiesis. 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. This gene encodes an EFNB class ephrin which binds to the EPHB4 and EPHA3 receptors. [provided by RefSeq, Jul 2008]
General function
Ligand, Growth factor
Comment
Cellular localization
Plasma membrane
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Ovarian function
Early embryo development
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New candidate genes to predict pregnancy outcome in single embryo transfer cycles when using cumulus cell gene expression. Wathlet S et al. OBJECTIVE: To relate the gene expression in cumulus cells surrounding an oocyte to the potential of the oocyte, as evaluated by the embryo morphology (days 3 and 5) and pregnancy obtained in single-embryo transfer cycles. DESIGN: Retrospective analysis of individual human cumulus complexes using quantitative real-time polymerase chain reaction for 11 genes. SETTING: University hospital IVF center. PATIENT(S): Thirty-three intracytoplasmic sperm injection patients, of which 16 were pregnant (4 biochemical and 12 live birth). INTERVENTION(S): Gene expression analysis in human cumulus complexes collected individually at pickup, allowing a correlation with the outcome of the corresponding oocyte. Multiparametric models were built for embryo morphology parameters and pregnancy prediction to find the most predictive genes. MAIN OUTCOME MEASURE(S): Gene expression profile of 99 cumulus complexes for 11 genes. RESULT(S): For embryo morphology prediction, TRPM7, ITPKA, STC2, CYP11A1, and HSD3B1 were often retained as informative. Models for pregnancy-biochemical or live birth-complemented or not with patient and cycle characteristics, always retained EFNB2 and CAMK1D together with STC1 or STC2. Positive and negative predictive values of the live birth models were >85%. CONCLUSION(S): EFNB2 and CAMK1D are promising genes that could help to choose the embryo to transfer with the highest chance of a pregnancy.
Expression regulated by
Comment
Ovarian localization
Cumulus, Granulosa, Luteal cells
Comment
Egawa M, et al reported that Ephrin B1 Is Expressed on Human Luteinizing Granulosa Cells in Corpora Lutea of the Early Luteal Phase:and the Possible Involvement of the B Class Eph-Ephrin System during Corpus Luteum Formation.
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Ephrins and their Eph receptors are both membrane-bound proteins that function in various cell-cell recognition processes, such as morphogenesis and angiogenesis. In this study we examined the expression of B class ephrins-Ephs in the human ovary during corpus luteum formation, a process of tissue remodeling accompanied by angiogenesis. RT-PCR analysis detected mRNAs for Eph B1, B2, and B4 and ephrin B1 and B2, but not Eph B3 and B6 or ephrin B3, in human corpora lutea of the early luteal phase. By immunohistochemistry, ephrin B1 was moderately expressed on theca interna cells, but was expressed at a low level on granulosa cells in the preovulatory follicles. After ovulation, a rapid increase in ephrin B1 expression was observed on luteinizing granulosa cells, whereas its expression on luteinizing theca interna cells decreased. The mRNA expression of ephrin B1 in luteinizing granulosa cells was confirmed by Northern blotting. Flow cytometry showed that ephrin B1 was expressed on the surface of isolated luteinizing granulosa cells. Moreover, these cells had the ability to bind to recombinant Eph B2-Fc fusion protein. These findings suggest that ephrin B1-expressing granulosa cells can directly interact with Eph-bearing cells during corpus luteum formation in vivo, suggesting that Eph-ephrin system is involved in this process.
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.