title: Eph receptor interclass cooperation is required for the regulation of cell proliferation.
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.
authors: Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors: Aleksandra
authors: A
authors: Jurek
authors: Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors: Maria
authors: M
authors: Genander
authors: 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.
authors: Parag
authors: P
authors: Kundu
authors: Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas TX 75390, USA.
authors: Timothy
authors: T
authors: Catchpole
authors: Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors: Xiao
authors: X
authors: He
authors: Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors: Klas
authors: K
authors: Strååt
authors: Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors: Hanna
authors: H
authors: Sabelström
authors: Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas TX 75390, USA.
authors: Nan-Jie
authors: NJ
authors: Xu
authors: 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.
authors: Sven
authors: S
authors: Pettersson
authors: Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas TX 75390, USA.
authors: Mark
authors: M
authors: Henkemeyer
authors: Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden. Electronic address: jonas.frisen@ki.se.
authors: Jonas
authors: J
authors: Frisén
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D036387:Ephrin-B1 / Q000378:metabolism; D036388:Ephrin-B2 / Q000378:metabolism; D006801:Humans; D007422:Intestines / Q000166:cytology; D007700:Kinetics; D008297:Male; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D059748:Proteolysis; D036081:Receptors, Eph Family / Q000378:metabolism*; D015398:Signal Transduction; D055153:Stem Cell Niche; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D036387:Ephrin-B1; D036388:Ephrin-B2; D036081:Receptors, Eph Family
keywords: Eph receptors; Ephrins; Intestinal stem cell niche; Proliferation