Fibroblast Growth Factor Receptor-induced Phosphorylation of EphrinB1 Modulates Its Interaction with Dishevelled

Lee, Hyun‐Shik; Mood, Kathleen; Battu, Gopala; Ji, Yon Ju; Singh, Arvinder; Daar, Ira

doi:10.1091/mbc.e08-06-0662

Cited by 46 publications

(56 citation statements)

References 47 publications

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“…Furthermore, activation of FGF signaling has a cell-autonomous role in controlling cell sorting in the mes. Finally, previous studies have shown that Fgfr1 is required for the expression of Cdh22, which encodes the cell adhesion molecule PB-cadherin, in the posterior mes (Trokovic et al, 2003), and that FGF signaling modulates ephrin and catenins in regulating cell-cell interactions (Lee et al, 2009;Lee et al, 2008;Lilien et al, 2002). As Fgf8-expressing cells form a tight transverse band in the isthmus, the mes cells immediately anterior to the MHB probably receive high levels of Fgf8 and thus display distinct cell adhesive characteristics.…”

Section: The Sorting Of Gbx2mentioning

confidence: 87%

Gbx2 and Fgf8 are sequentially required for formation of the midbrain-hindbrain compartment boundary

Sunmonu

Guo

2011

Development

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SUMMARYIn vertebrates, the common expression border of two homeobox genes, Otx2 and Gbx2, demarcates the prospective midbrainhindbrain border (MHB) in the neural plate at the end of gastrulation. The presence of a compartment boundary at the MHB has been demonstrated, but the mechanism and timing of its formation remain unclear. We show by genetic inducible fate mapping using a Gbx2CreER knock-in mouse line that descendants of Gbx2 + cells as early as embryonic day (E) 7.5 do not cross the MHB. Without Gbx2, hindbrain-born cells abnormally populate the entire midbrain, demonstrating that Gbx2 is essential for specifying hindbrain fate. Gbx2 + and Otx2 + cells segregate from each other, suggesting that mutually exclusive expression of Otx2 and Gbx2 in midbrain and hindbrain progenitors is responsible for cell sorting in establishing the MHB. The MHB organizer gene Fgf8, which is expressed as a sharp transverse band immediately posterior to the lineage boundary at the MHB, is crucial in maintaining the lineage-restricted boundary after E7.5. Partial deletion of Fgf8 disrupts MHB lineage separation. Activation of FGF pathways has a cell-autonomous effect on cell sorting in midbrain progenitors. Therefore, Fgf8 from the MHB may signal the nearby mesencephalic cells to impart distinct cell surface characteristics or induce local cell-cell signaling, which consequently prevents cell movements across the MHB. Our findings reveal the distinct function of Gbx2 and Fgf8 in a stepwise process in the development of the compartment boundary at the MHB and that Fgf8, in addition to its organizer function, plays a crucial role in maintaining the lineage boundary at the MHB by restricting cell movement.

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Section: The Sorting Of Gbx2mentioning

confidence: 87%

Gbx2 and Fgf8 are sequentially required for formation of the midbrain-hindbrain compartment boundary

Sunmonu

Guo

2011

Development

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“…Members of the ephrinB family are often overexpressed in cancer cells and are associated with angiogenesis and metastasis (45). Although several studies provide insight into how ephrinB1-mediated reverse signaling contributes to invasion of gastric and pancreas cancer cells (46,47), recent evidence reveals that intracellular domain of ephrinB1 interacts with Dvl and modulates PCP signaling to control cell adhesion and movement in development (48)(49)(50). This opens up the possibility to explore the potential crosstalk between ephrinB and PCP signaling in the context of tumor cell invasion and metastasis.…”

Section: Role Of Pcp Signaling In Tumor Metastasismentioning

confidence: 99%

Wnt/Planar cell polarity signaling: A new paradigm for cancer therapy

Wang

2009

Molecular Cancer Therapeutics

189

182

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The evolutionarily conserved and developmentally important Wnt signaling pathway has traditionally been regarded as a critical player in tumorigenesis through the canonical Wnt/β-catenin cascade. Nevertheless, accumulating evidence based on recent research has revealed the previously unacknowledged role of noncanonical Wnt/planar cell polarity (PCP) signaling in cancer progression, invasion and metastasis, and angiogenesis. This review describes the PCP signaling pathway and its ever-expanding components and modulators, highlights the most recent studies that provide insight into the link between PCP signaling and cancer, and, finally, proposes a model by which PCP signaling may promote cancer development. This review underscores the emerging theme that deregulated PCP signaling contributes to tumorigenesis, providing new potential targets for cancer therapy.

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“…The ephrinB1 DV mutant construct harbors a deletion of the conserved C-terminal valine that has been demonstrated to be critical for the binding of PDZ domain-containing proteins to both ephrin-B1 and ephrin-B2 (Lin et al 1999;Makinen et al 2005). It has been suggested that phosphorylation-dependent and PDZ-dependent reverse signaling may cooperate to achieve reverse signaling outcomes (Palmer et al 2002;Su et al 2004;Lee et al 2009). To address this possibility, we also generated a mutant mouse line in which the intracellular tyrosines Previous work has demonstrated the importance of proper membrane localization for evaluation of reverse signaling function Makinen et al 2005).…”

Section: Fmentioning

confidence: 99%

Ephrin-B1 regulates axon guidance by reverse signaling through a PDZ-dependent mechanism

Bush¹,

Soriano²

2009

Genes Dev.

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Mutations in the ephrin-B1 gene result in craniofrontonasal syndrome (CFNS) in humans, a congenital disorder that includes a wide range of craniofacial, skeletal, and neurological malformations. In addition to the ability of ephrin-B1 to forward signal through its cognate EphB tyrosine kinase receptors, ephrin-B1 can also act as a receptor and transduce a reverse signal by either PDZ-dependent or phosphorylation-dependent mechanisms. To investigate how ephrin-B1 acts to influence development and congenital disease, we generated mice harboring a series of targeted point mutations in the ephrin-B1 gene that independently ablate specific reverse signaling pathways, while maintaining forward signaling capacity. We demonstrate that both PDZ and phosphorylationdependent reverse signaling by ephrin-B1 are dispensable for craniofacial and skeletal development, whereas PDZdependent reverse signaling by ephrin-B1 is critical for the formation of a major commissural axon tract, the corpus callosum. Ephrin-B1 is strongly expressed within axons of the corpus callosum, and reverse signaling acts autonomously in cortical axons to mediate an avoidance response to its signaling partner EphB2. These results demonstrate the importance of PDZ-dependent reverse signaling for a subset of Ephrin-B1 developmental roles in vivo. The capacity for bidirectional signaling is a hallmark of the Eph/ephrin signaling system: In addition to their ability to signal through cognate Eph tyrosine kinase receptors, ephrins can also transduce a reverse signal into the cell in which they are expressed (Davy and Soriano 2005). Bidirectional signaling can occur for both A-and B-type subfamilies, although the mechanisms by which ephrins accomplish this reverse signal differ. Ephrin-As are tethered to the membrane via a GPI linkage, whereas ephrin-Bs are transmembrane molecules and possess a conserved intracellular domain. Ephrin-B1, a member of the B-type subfamily, can bind EphB1-3, although genetic studies comparing phenotypes of mice harboring loss-of-function mutations in the receptors and ligands suggest that EphB2 and EphB3 are the principal receptors for ephrin-B1 in most developmental contexts Compagni et al. 2003;Blits-Huizinga et al. 2004). The capacity for bidirectional signaling was initially identified based on discordances between phenotypes observed in complete loss-of-function mutations of EphB2 compared with mutations in which only the kinase domain of EphB2 was mutated, leaving the extracellular portion intact . Whereas EphB2 homozygous null mutant mice displayed defects in the axon pathfinding of the anterior commissure, EphB2 mutants lacking kinase activity did not display these defects, indicating that kinase activity was not required for EphB2s role in anterior commissure formation . Direct genetic evidence for reverse signaling has since been obtained by the analysis of mutations in B-type ephrins that abrogate reverse signaling while maintaining forward signaling capacity; however, the relative importance and mechanism of action o...

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Fibroblast Growth Factor Receptor-induced Phosphorylation of EphrinB1 Modulates Its Interaction with Dishevelled

Cited by 46 publications

References 47 publications

Gbx2 and Fgf8 are sequentially required for formation of the midbrain-hindbrain compartment boundary

Gbx2 and Fgf8 are sequentially required for formation of the midbrain-hindbrain compartment boundary

Wnt/Planar cell polarity signaling: A new paradigm for cancer therapy

Ephrin-B1 regulates axon guidance by reverse signaling through a PDZ-dependent mechanism

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