Ectopic EphA4 receptor induces posterior protrusions via FGF signaling in Xenopus embryos
Eui Kyun Park,Neil Warner,Neil Warner,Yong-Sik Bong,David Stapleton,Ryu Maeda,Tony Pawson,Tony Pawson,Ira O. Daar +8 more
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TLDR
Analysis of double mutants revealed that the Y928F EphA4 phenotypes were dependent on kinase activity; juxtamembrane sites of tyrosine phosphorylation and SH2 domain-binding were required for cell dissociation, but not for posterior protrusions.Abstract:
The Eph family of receptor tyrosine kinases regulates numerous biological processes. To examine the biochemical and developmental contributions of specific structural motifs within Eph receptors, wild-type or mutant forms of the EphA4 receptor were ectopically expressed in developing Xenopus embryos. Wild-type EphA4 and a mutant lacking both the SAM domain and PDZ binding motif were constitutively tyrosine phosphorylated in vivo and catalytically active in vitro. EphA4 induced loss of cell adhesion, ventro-lateral protrusions, and severely expanded posterior structures in Xenopus embryos. Moreover, mutation of a conserved SAM domain tyrosine to phenylalanine (Y928F) enhanced the ability of EphA4 to induce these phenotypes, suggesting that the SAM domain may negatively regulate some aspects of EphA4 activity in Xenopus. Analysis of double mutants revealed that the Y928F EphA4 phenotypes were dependent on kinase activity; juxtamembrane sites of tyrosine phosphorylation and SH2 domain-binding were required for cell dissociation, but not for posterior protrusions. The induction of protrusions and expansion of posterior structures is similar to phenotypic effects observed in Xenopus embryos expressing activated FGFR1. Furthermore, the budding ectopic protrusions induced by EphA4 express FGF-8, FGFR1, and FGFR4a. In addition, antisense morpholino oligonucleotide-mediated loss of FGF-8 expression in vivo substantially reduced the phenotypic effects in EphA4Y928F expressing embryos, suggesting a connection between Eph and FGF signaling.read more
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The Many Faces of SAM
Feng Qiao,James U. Bowie +1 more
TL;DR: This review describes the structural basis of SAM domain interactions and highlights their roles in the scaffolding of protein complexes in normal and pathological processes, and aims to know how to predict any SAM domain.
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Eph/ephrin signaling: networks
Dina N. Arvanitis,Alice Davy +1 more
TL;DR: In vitro and in vivo data describing molecular, functional, and genetic interactions between Eph/ephrin and other cell surface signaling pathways are reviewed.
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EphA1 interacts with integrin-linked kinase and regulates cell morphology and motility
TL;DR: It is shown that activation of EphA1 kinase inhibits cell spreading and migration in a RhoA-ROCK-dependent manner and a novel interaction between Eph a1 and integrin-linked kinase (ILK), a mediator of interactions between integrin and the actin cytoskeleton.
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Eph-dependent cell-cell adhesion and segregation in development and cancer
TL;DR: This review summarises the current understanding of how Eph receptors control cell adhesion and morphology, and presents examples demonstrating the importance of these events in normal development and cancer.
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Concepts and consequences of Eph receptor clustering.
TL;DR: Emerging evidence is reviewed suggesting that the required combinatorial diversity is not only achieved by the large number of possible Eph-ephrin interactions and selective use of Eph forward and ephrin reverse signals, but in particular through the composition and signal capacity of EPh-epHRin clusters, which is adjusted dynamically to reflect overall Eph and Ephrin surface densities on interacting cells.
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