Ephrins and their Receptors: Binding versus Biology

Blits-Huizinga, Carla T.; Nelersa, Claudiu M.; Malhotra, Arun; Liebl, Daniel J.

doi:10.1080/15216540412331270076

Cited by 66 publications

(87 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EphrinB3 KO mice have significant defects in CC midline crossing that are not observed in the ephrinB3 lacZ knock-in mice, suggesting that forward signaling through Eph receptor(s) is important. EphB2 and EphB3 receptors are all potential binding partners for ephrinB3 and have the possibility of mediating this forward signaling (Blits-Huizinga et al, 2004). Previous investigations have evaluated ephrinB3 KO mice and report that ϳ20% of knock-out mice have CC agenesis (Yokoyama et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Multiple Eph Receptors and B-Class Ephrins Regulate Midline Crossing of Corpus Callosum Fibers in the Developing Mouse Forebrain

Mendes¹,

Henkemeyer²,

Liebl³

2006

J. Neurosci.

105

View full text Add to dashboard Cite

Agenesis of the corpus callosum (CC) is a rare birth defect that occurs in isolated conditions and in combination with other developmental cerebral abnormalities. Recent identification of families of growth and guidance molecules has generated interest in the mechanisms that regulate callosal growth. One family, ephrins and Eph receptors, has been implicated in mediating midline pathfinding decisions; however, the complexity of these interactions has yet to be unraveled. Our studies shed light on which B-class ephrins and Eph receptors function to regulate CC midline growth and how these molecules interact with important guideposts during development. We show that multiple Eph receptors (B1, B2, B3, and A4) and B-class ephrins (B1, B2, and B3) are present and function in developing forebrain callosal fibers based on both spatial and temporal expression patterns and analysis of gene-targeted knock-out mice. Defects are most pronounced in the combination double knock-out mice, suggesting that compensatory mechanisms exist for several of these family members. Furthermore, these CC defects range from mild hypoplasia to complete agenesis and Probst's bundle formation. Further analysis revealed that Probst's bundle formation may reflect aberrant glial formations and/or altered sensitivity of CC axons to other guidance cues. Our results support a significant role for ephrins and Eph receptors in CC development and may provide insight to possible mechanisms involved in axon midline crossing and human disorder.

show abstract

Section: Discussionmentioning

confidence: 99%

Multiple Eph Receptors and B-Class Ephrins Regulate Midline Crossing of Corpus Callosum Fibers in the Developing Mouse Forebrain

Mendes¹,

Henkemeyer²,

Liebl³

2006

J. Neurosci.

105

View full text Add to dashboard Cite

show abstract

“…The fact that the Eph family constitutes the largest family of known tyrosine kinase receptors together with the promiscuity of Eph-ephrin binding, although presenting different ligand-receptor affinities, makes this family of proteins a plastic system for multiple possible interactions. Furthermore, although in many cases the system seems to be redundant, the different affinities and patterns of expression suggest a certain specialization and the possibility of regulating a wide spectrum of cell functions [13,14].…”

Section: Introductionmentioning

confidence: 99%

EphrinB1‐EphB signaling regulates thymocyte‐epithelium interactions involved in functional T cell development

et al. 2007

View full text Add to dashboard Cite

The Eph and ephrin families are involved in numerous developmental processes. Recently, an increasing body of evidence has related these families with some aspects of T cell development. In the present study, we show that the addition of either EphB2-Fc or ephrinB1-Fc fusion proteins to fetal thymus organ cultures established from 17-dayold fetal mice decreases the numbers of both double-positive (CD4 + CD8 + ) and singlepositive (both CD4 + CD8 -and CD4 -CD8 + ) thymocytes, in correlation with increased apoptosis. By using reaggregate thymus organ cultures formed by fetal thymic epithelial cells (TEC) and CD4 + CD8 + thymocytes, we have also demonstrated that ephrinB1-Fc proteins are able to disorganize the three-dimensional epithelial network that in vivo supports the T cell maturation, and to alter the thymocyte interactions. In addition, in an in vitro model, Eph/ephrinB-Fc treatment also decreases the formation of cell conjugates by CD4 + CD8 + thymocytes and TEC as well as the TCR-dependent signaling between both cell types. Finally, immobilized EphB2-Fc and ephrinB1-Fc modulate the anti-CD3 antibody-induced apoptosis of CD4 + CD8 + thymocytes in a process dependent on concentration. These results therefore support a role for Eph/ephrinB in the processes of development and selection of thymocytes as well as in the establishment of the three-dimensional organization of TEC.

show abstract

“…In mammals, EphA receptors (EphA1-8, EphA10) promiscuously bind ephrin-A proteins (ephrin-A1-6), and EphB receptors (EphB1-4, EphB6) interact in a similar manner with three ephrin-Bs (ephrin-B1-3) (31). This rule, however, is not without exceptions, because EphA4 is capable of binding ephrin-Bs, and EphB2 can be activated by ephrin-A5 in addition to their conventional ephrin-A and ephrin-B ligands (32)(33)(34)(35)(36). In contrast, EphB6 interactions appear to be restricted to ephrin-B1 and ephrin-B2 (34,37,38).…”

mentioning

confidence: 92%

“…Because Eph receptors have been shown to initiate antiapoptotic responses in nonlymphoid malignancies (25)(26)(27)(28)(29)(30), we examined the ability of EphB receptors to interfere with FasR-initiated cell death in malignant T cells. To assess the effect of EphBs, we stimulated H9 and Molt-16 cells with the activating anti-FasR Ab, 7C11, alone or in the presence of increasing concentrations of the common ligand for EphB3 and EphB6, ephrin-B2 (34,38). Because an ephrin-B2-Fc fusion protein, with the extracellular portion of the ligand fused to the Fc fragment of hIgG, was used, hIgG was introduced as a specificity control.…”

Section: Ephb Receptors Are Expressed By Malignant T Cells and Protecmentioning

confidence: 99%

“…This rule, however, is not without exceptions, because EphA4 is capable of binding ephrin-Bs, and EphB2 can be activated by ephrin-A5 in addition to their conventional ephrin-A and ephrin-B ligands (32)(33)(34)(35)(36). In contrast, EphB6 interactions appear to be restricted to ephrin-B1 and ephrin-B2 (34,37,38). All ephrins are membraneattached proteins; ephrin-As are GPI-anchored, whereas ephrin-Bs have transmembrane and cytoplasmic domains, and their membrane localization appears to be crucial for their ability to trigger Eph signaling (39).…”

mentioning

confidence: 99%

See 1 more Smart Citation

EphB Receptors Trigger Akt Activation and Suppress Fas Receptor-Induced Apoptosis in Malignant T Lymphocytes

Maddigan

Truitt

Arsenault

et al. 2011

The Journal of Immunology

View full text Add to dashboard Cite

Treatment of hematopoietic malignancies often requires allogeneic bone marrow transplantation, and the subsequent graft-versus-leukemia response is crucial for the elimination of malignant cells. Cytotoxic T lymphocytes and NK cells responsible for the immunoelimination express Fas ligand and strongly rely on the induction of Fas receptor-mediated apoptosis for their action. Although cancer cells are removed successfully by graft-versus-leukemia reactions in myeloid malignancies, their efficiency is low in T cell leukemias. This may be partially because of the ability of malignant T cells to escape apoptosis. Our work shows that Eph family receptor EphB3 is consistently expressed by malignant T lymphocytes, most frequently in combination with EphB6, and that stimulation with their common ligands, ephrin-B1 and ephrin-B2, strongly suppresses Fas-induced apoptosis in these cells. This effect is associated with Akt activation and with the inhibition of the Fas receptor-initiated caspase proteolytic cascade. Akt proved to be crucial for the prosurvival response, because inhibition of Akt, but not of other molecules central to T cell biology, including Src kinases, MEK1 and MEK2, blocked the antiapoptotic effect. Overall, this demonstrates a new role for EphB receptors in the protection of malignant T cells from Fas-induced apoptosis through Akt engagement and prevention of caspase activation. Because Fas-triggered apoptosis is actively involved in the graft-versus-leukemia response and cytotoxic T cells express ephrin-Bs, our observations suggest that EphB receptors are likely to support immunoevasivenes of T cell malignancies and may represent promising targets for therapies, aiming to enhance immunoelimination of cancerous T cells.

show abstract

Ephrins and their Receptors: Binding versus Biology

Cited by 66 publications

References 46 publications

Multiple Eph Receptors and B-Class Ephrins Regulate Midline Crossing of Corpus Callosum Fibers in the Developing Mouse Forebrain

Multiple Eph Receptors and B-Class Ephrins Regulate Midline Crossing of Corpus Callosum Fibers in the Developing Mouse Forebrain

EphrinB1‐EphB signaling regulates thymocyte‐epithelium interactions involved in functional T cell development

EphB Receptors Trigger Akt Activation and Suppress Fas Receptor-Induced Apoptosis in Malignant T Lymphocytes

Contact Info

Product

Resources

About