Eph receptor interclass cooperation is required for the regulation of cell proliferation

Aleksandra Jurek, Maria Genander, Parag Kundu, Timothy Catchpole, Xiao He, Klas Strååt, Hanna Sabelström, Nan Jie Xu, Sven Pettersson, Mark Henkemeyer, Jonas Frisén

Research output: Contribution to journalArticle

4 Scopus citations

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 languageEnglish (US)
Pages (from-to)10-22
Number of pages13
JournalExperimental Cell Research
Volume348
Issue number1
DOIs
StatePublished - Oct 15 2016

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Keywords

  • Eph receptors
  • Ephrins
  • Intestinal stem cell niche
  • Proliferation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Jurek, A., Genander, M., Kundu, P., Catchpole, T., He, X., Strååt, K., Sabelström, H., Xu, N. J., Pettersson, S., Henkemeyer, M., & Frisén, J. (2016). Eph receptor interclass cooperation is required for the regulation of cell proliferation. Experimental Cell Research, 348(1), 10-22. https://doi.org/10.1016/j.yexcr.2016.08.017