Ephrin‐B2 is a candidate ligand for the Eph receptor, EphB6

Munthe, Else; Rian, Edith; Holien, Toril; Rasmussen, Anne Marie; Levy, Finn Olav; Aasheim, Hans Christian

doi:10.1016/s0014-5793(99)01793-7

Cited by 43 publications

(29 citation statements)

References 49 publications

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“…Munthe et al (25) recently reported that ephrinB2 is a candidate ligand for EphB6 according to cell surface binding assays. In a separate study, we performed in situ hybridization on the expression patterns of mouse ephrinB2 and EphB6 and found that their expression was colocalized in white pulp of the spleen and cortex of the thymus (data not shown), unlike reciprocal expression patterns between other Eph kinases and their ligands in the CNS or vascular system.…”

Section: Discussionmentioning

confidence: 99%

Cross-Linking of EphB6 Resulting in Signal Transduction and Apoptosis in Jurkat Cells

Luo

Wan

et al. 2001

The Journal of Immunology

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Eph kinases are the largest family of receptor tyrosine kinases (RTK), and their ligands are cell surface molecules. The known functions of Eph kinases are mainly pattern formation in the CNS. Although several Eph kinases are expressed at high levels in hemopoietic cells and in the thymus, we have no knowledge of the functions of any Eph kinase in the immune system. In this study, we have demonstrated that an Eph kinase, EphB6, was expressed at high levels in Jurkat leukemic T cells. Co-cross-linking of EphB6 and CD3 led to an altered profile of lymphokine secretion along with proliferation inhibition of Jurkat cells. The cells subsequently underwent Fas-mediated apoptosis. Although EphB6 has no intrinsic kinase activity, its cross-linking triggered general protein tyrosine phosphorylation in Jurkat cells. EphB6 was found to associate with a number of molecules in the signaling pathways, notably Cbl. EphB6 cross-linking resulted in Cbl dephosphorylation and dissociation from Src homology 2 domain-containing tyrosine phosphatase-1 (SHP-1). Our results show that EphB6 has important functions in T cells, and it can transduce signals into the cells via proteins it associates with.

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Section: Discussionmentioning

confidence: 99%

Cross-Linking of EphB6 Resulting in Signal Transduction and Apoptosis in Jurkat Cells

Luo

Wan

et al. 2001

The Journal of Immunology

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“…HEK-293T cells were transfected using the calcium phosphate precipitation method, and HeLa cells were transfected using FuGENE6 Transfection Reagent (Roche Applied Sciences, Penzberg, Germany). EphrinA5-Fc fusion protein was generated as described earlier (Munthe et al, 2000), and the primer pair for the construct was: F: 5 0 -CATAAGCTTC CACCATGTTGCACGTGGAGATGTT-3 0 , R: 5 0 -ATCGGAT CCTGACTCATGTACGGTGTC-3 0 .…”

Section: Plasmids Construction and Cell Transfectionmentioning

confidence: 99%

EphrinA5 acts as a tumor suppressor in glioma by negative regulation of epidermal growth factor receptor

et al. 2009

Oncogene

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Eph receptors, the largest subfamily of receptor tyrosine kinases, and their ephrin ligands play important roles in nervous system development. Recently, they have been implicated in tumorigenesis of different cancers. In this study, we showed that the expression of ephrinA5 was dramatically downregulated in primary gliomas compared with normal tissues. Forced expression of ephrinA5 reduced tumorigenicity of human glioma U373 cells. Epidermal growth factor receptor (EGFR), which frequently acts as an oncoprotein in glioma, was greatly decreased in ephrinA5-transfected glioma cells, and the two molecules exhibited a mutually exclusive expression pattern in primary glioma samples. We found that ephrinA5 enhanced c-Cbl binding to EGFR, thus promoted ubiquitylation and degradation of the receptor. Either ephrinA5-Fc or EphA2-Fc treatment simulating bidirectional signaling of Eph/ephrin system resulted in EGFR decrease. This study discovered that ephrinA5 acted as a tumor suppressor in glioma, and its negative regulation of EGFR contributed to the suppressive effects. In addition to identifying a novel mechanism underlying tumor suppressor activity of ephrinA5, we also showed cross-talk between different receptor tyrosine kinase families in glioma. These findings may improve therapeutic strategies for glioma.

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“…The EphB6 cDNA was first cloned from normal human brain RNA and its protein product has since been shown to be involved in T-cell function (Matsuoka et al, 1997;Luo et al, 2001;Freywald et al, 2003). EphB6, although kinase deficient, is a target for phosphorylation by EphB1 following stimulation with ephrinB1 or ephrinB2 (Munthe et al, 2000;Freywald et al, 2002;Matsuoka et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

EphB6 receptor significantly alters invasiveness and other phenotypic characteristics of human breast carcinoma cells

Fox

Kandpal

2009

Oncogene

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Breast cancer mortality in women is largely attributed to the metastasis of primary breast tumors. We have analysed the function of EphB6, a kinase-deficient receptor, in the invasive phenotype of breast cancer cell lines. We have demonstrated the loss of EphB6 protein in invasive breast carcinoma cell lines and absence of EphB6 transcript in a metastatic breast tumor specimen. The function of EphB6 in invasiveness was confirmed by the ability of EphB6 protein to decrease the in vitro invasiveness of MDA-MB-231, MDA-MB-435 and BT549 cells transfected with an EphB6 expression construct. In MDA-MB-231 cells, the decreased invasiveness appeared to be mediated by decreased transcript levels of matrix metalloproteinase (MMP)7 and MMP19, and increased transcript levels of tissue inhibitors of metalloproteinase 2. In addition to affecting invasiveness phenotype, EphB6 overexpression was also responsible for altering the growth rate and colony-forming efficiency of MCF-7 and MDA-MB-231 cells in a cell-line-specific manner. We suggest that the significant decrease in the invasiveness of MDA-MB-231 and other cell lines transfected with EphB6 is likely occurring by the ability of EphB6 to transduce signals to the nucleus and altering relevant gene expression.

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Ephrin‐B2 is a candidate ligand for the Eph receptor, EphB6

Cited by 43 publications

References 49 publications

Cross-Linking of EphB6 Resulting in Signal Transduction and Apoptosis in Jurkat Cells

Cross-Linking of EphB6 Resulting in Signal Transduction and Apoptosis in Jurkat Cells

EphrinA5 acts as a tumor suppressor in glioma by negative regulation of epidermal growth factor receptor

EphB6 receptor significantly alters invasiveness and other phenotypic characteristics of human breast carcinoma cells

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