Format

Send to

Choose Destination
Exp Cell Res. 2016 Oct 15;348(1):10-22. doi: 10.1016/j.yexcr.2016.08.017. Epub 2016 Aug 24.

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

Author information

1
Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
2
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden; Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551; Lee Kong Chian School of Medicine, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.
3
Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas TX 75390, USA.
4
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden; Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551; Lee Kong Chian School of Medicine, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551; The National Cancer Centre, Singapore General Hospital, Singapore.
5
Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden. Electronic address: jonas.frisen@ki.se.

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.

KEYWORDS:

Eph receptors; Ephrins; Intestinal stem cell niche; Proliferation

PMID:
27565439
DOI:
10.1016/j.yexcr.2016.08.017
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center