Abstract
Cancer often arises by the constitutive activation of mitogenic pathways by mutations in stem cells. Eph receptors are unusual in that although they regulate the proliferation of stem/progenitor cells in many adult organs, they typically fail to transform cells. Multiple ephrins and Eph receptors are often co-expressed and are thought to be redundant, but we here describe an unexpected dichotomy with two homologous ligands, ephrin-B1 and ephrin-B2, regulating specifically migration or proliferation in the intestinal stem cell niche. We demonstrate that the combined activity of two different coexpressed Eph receptors of the A and B class assembled into common signaling clusters in response to ephrin-B2 is required for mitogenic signaling. The requirement of two different Eph receptors to convey mitogenic signals identifies a new type of cooperation within this receptor family and helps explain why constitutive activation of a single receptor fails to transform cells.
Original language | English (US) |
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Pages (from-to) | 10-22 |
Number of pages | 13 |
Journal | Experimental Cell Research |
Volume | 348 |
Issue number | 1 |
DOIs | |
State | Published - Oct 15 2016 |
Keywords
- Eph receptors
- Ephrins
- Intestinal stem cell niche
- Proliferation
ASJC Scopus subject areas
- Cell Biology