Disease relevance of EPHB4

• HTK (hepatoma transmembrane kinase) is a receptor tyrosine kinase belonging to the EPH subfamily of tyrosine kinases [1].
• Rat livers were harvested after 45 min of cardiac arrest and preserved in HTK solution for 24 h [2].
• Fatty livers were retrieved, flushed and then stored at 4 degrees C for 24 hours with either HTK or Polysol [3].
• In conclusion, the preservation solution that is the least harmful to endothelial cells at hypothermia is Bretschneider HTK cardioplegic solution [4].
• Various breast cancer cell lines can efficiently synthesize HTK from the translationally regulated mRNA, whereas normal cells cannot [5].
• We provide mechanistic evidence showing that promoter methylation regulates EPHB4 transcription and functional evidence that EPHB4 can regulate the long-term clonogenic potential of colorectal tumor cells, revealing EPHB4 as a potential new tumor suppressor gene in colorectal cancer [6].

High impact information on EPHB4

• Receptor tyrosine kinase, EphB4 (HTK), accelerates differentiation of select human hematopoietic cells [7].
• Immunohistochemical analysis of one of the newly identified correlated L-R pairs (i.e., EFNB3-EPHB4) revealed the correlated expression of ephrin-B3 and EphB4 proteins in 45 of 55 epithelial ovarian tumor samples (P < 0.0001) [8].
• In vitro cytotrophoblasts avoided EPHB4-coated substrates; upon co-culture with 3T3 cells expressing this molecule, their migration was significantly inhibited [9].
• When cytotrophoblasts encounter EPHB4 expressed by venous endothelium, ephrin B-generated repulsive signals and a reduction in chemokine-mediated responses limit their interaction with veins [9].
• Additionally, cytotrophoblast commitment to uterine invasion was accompanied by rapid downregulation of EPHB4, a transmembrane receptor associated with venous identity, and upregulation of ephrin B1 [9].

Chemical compound and disease context of EPHB4

• Expression of receptor tyrosine kinase HTK (hepatoma transmembrane kinase) and HTK ligand by human leukemia-lymphoma cell lines [1].
• There was good correlation between the amount of PCR-amplified product and the number of colony forming units when glioma cells were transduced with the retroviruses containing both the neomycin resistance gene and the HTK gene [10].
• Our results suggest that repeated inoculations of high-titer retroviruses carrying the HTK gene followed by GCV treatment may be a promising strategy for the clinical treatment of malignant gliomas [11].

Biological context of EPHB4

• Six of 7 (86%) HNSCC cell lines express EphB4, which is induced either by EGFR activation or by EPHB4 gene amplification [12].
• The HTK gene is located on human chromosome 7 [13].
• Binding of its ligand (HTKL) results in tyrosine phosphorylation of HTK [1].
• In the present study, we analyzed the possible involvement of this ligand-receptor signalling system in hematopoiesis by examining the expression of both HTK and HTKL in a large and comprehensive panel of 70 continuous human leukemia-lymphoma cell lines [1].
• Investigation of the details of signal transduction pathway that is activated by the HTK tyrosine kinase will help to define the exact biological function of the HTK-HTKL system [1].

Anatomical context of EPHB4

• We propose that EPHB4/ephrin B1 interactions generate repulsive signals that direct cytotrophoblast invasion toward the uterus, where chemokines stimulate cytotrophoblast migration through the decidua [9].
• METHODS: Ten and 11 liver grafts were perfused via the portal vein with University of Wisconsin solutions (UW group) and Bretschneider's Histidine-Tryptophan-Ketoglutarate solutions (HTK group), respectively [14].
• When cultured hepatocytes were incubated in HTK solution or in modified Krebs-Henseleit buffer containing 198 mM L-histidine at 37 degrees C, most cells lost viability within 3 h (LDH release 86 +/- 7% and 89 +/- 5%, respectively) [15].
• METHODS: A telomerase-infected, extended-lifespan human corneal fibroblast cell line (HTK) was transfected by using a vector for enhanced green fluorescent protein (GFP)-alpha-actinin [16].
• UW is superior to Celsior and HTK in the protection of human liver endothelial cells against preservation injury [17].

Associations of EPHB4 with chemical compounds

• Chemical modification experiments of cysteine residues have shown that the cysteine residues of HTK are less accessible to an SH reagent than those of the preevolved KNT [18].
• The superior protection provided by Bretschneider HTK was due to its additives histidine, tryptophan, and KH-2-oxygluterate (p less than 0.005), and to its low chloride content (p less than 0.005) [4].
• In Group A, in which ketoglutarate was excluded from the HTK solution, percent developed pressure was significantly decreased (p<0.01) and the released enzyme (CK-MB) was significantly increased, but coronary flow was not significantly changed [19].
• The aim of our study was to compare the protective effect of UW and HTK solutions on preservation-induced injury of jejunal grafts, as evaluated by the histological changes (semiquantitative method) and small bowel mucosal serotonin levels (as a possible new quantitative method) [20].
• Therefore, histidine-tryptophan-ketoglutarate solution (HTK; alpha-ketoglutarate) and University of Wisconsin solution (UW; adenosine) were supplied with energy substrates to achieve graft viability [21].

Other interactions of EPHB4

• Expression of Ephb2 and Ephb4 in breast carcinoma [22].

Analytical, diagnostic and therapeutic context of EPHB4

• Northern blot analysis demonstrated a single HTK transcript abundantly present in placenta and in a range of primary tissues and malignant cell lines [13].
• HTK and HTKL mRNA expression were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) [1].
• Does using HTK solution for cold perfusion of cadaveric kidneys save money [23]?
• Livers preserved for 24 hr using HTK showed life-supporting function after transplantation (n = 5, survival 12 hr-8 days) [24].
• HTK (histidine-tryptophane-ketoglutarate) organ preservation solution has been shown to be effective in human kidney transplantation, but the efficacy of HTK for extended liver preservation has not been determined [24].

References