Eph receptor and ephrin function in breast, gut, and skin epithelia

Abstract

Abbreviations: ADAM, a disintegrin and metalloprotease; Apc, adenomatous polyposis coli; Eph, erythropoietin-producing hepatocellular; ER, estrogen receptor; Erk, extracellular signal-regulated kinase; GEF, guanine nucleotide exchange factor; GPI, glycosylphosphatidylinositol; HER2, human epidermal growth factor receptor 2; HGF, hepatocyte growth factor; IBD, inflammatory bowel disease; KLF, Kr€ uppel-like factor; MAPK, mitogen-activated protein kinase; MMTV-LTR, mouse mammary tumor virus-long terminal repeat; MT1-MMP, membrane-type 1 matrix metalloproteinase; PDZ, postsynaptic density protein 95, discs large 1, and zonula occludens-1; PTP, protein tyrosine phosphatase; RTK, receptor tyrosine kinase; SH2, Src homology 2; SHIP2, SH2 inositol phosphatase 2; SLAP, Src-like adaptor protein; TCF, T-cell specific transcription factor; TEB, terminal end bud; TNFa, tumor necrosis factor a:Epithelial cells are tightly coupled together through specialized intercellular junctions, including adherens junctions, desmosomes, tight junctions, and gap junctions. A growing body of evidence suggests epithelial cells also directly exchange information at cell-cell contacts via the Eph family of receptor tyrosine kinases and their membrane-associated ephrin ligands. Ligand-dependent and -independent signaling via Eph receptors as well as reverse signaling through ephrins impact epithelial tissue homeostasis by organizing stem cell compartments and regulating cell proliferation, migration, adhesion, differentiation, and survival. This review focuses on breast, gut, and skin epithelia as representative examples for how Eph receptors and ephrins modulate diverse epithelial cell responses in a context-dependent manner. Abnormal Eph receptor and ephrin signaling is implicated in a variety of epithelial diseases raising the intriguing possibility that this cellcell communication pathway can be therapeutically harnessed to normalize epithelial function in pathological settings like cancer or chronic inflammation.

Novel Roles and Mechanism for Krüppel-like Factor 16 (KLF16) Regulation of Neurite Outgrowth and Ephrin Receptor A5 (EphA5) Expression in Retinal Ganglion Cells

“…Ligand binding activates bidirectional intracellular signaling through both the receptor and ligand, and it mediates a wide range of cellular activities (13)(14)(15)(16). In projection neurons such as RGCs, activation of EPH/EFN signaling reduces cell adhesion and leads to growth cone collapse (17).…”

Comparative Analysis of RNAi-Based Methods to Down-Regulate Expression of Two Genes Expressed at Different Levels in Myzus persicae

“…To confirm the role of these two genes in polerovirus transmission by aphids, it is necessary to efficiently and reproducibly inhibit expression of these genes in aphids before addressing the ability of these aphids to transmit the virus. ALY is a mRNA export factor which shuttles between the nucleus and the cytoplasm [40] and Eph plays a role in the maintenance of epithelial tissue homeostasis [41]. Both are expressed throughout the aphid body and in the gut, but ALY transcripts accumulated at a higher level compared to Eph transcripts.…”

EphA2 proteomics in human keratinocytes reveals a novel association with afadin and epidermal tight junctions

“…EphA2 interacts with ephrins on adjacent cells to regulate epithelial tissue homeostasis (Perez White and Getsios, 2014). Specifically, loss of EphA2 increased susceptibility to chemically-induced skin carcinogenesis (Guo et al, 2006), whereas ephrin-targeting of EphA2 enhanced keratinocyte adhesion and differentiation (Lin et al, 2010;Walsh and Blumenberg, 2011).…”