| Title | A motif in LILRB2 critical for Angptl2 binding and activation |
| Authors | Deng, Mi Lu, Zhigang Zheng, Junke Wan, Xuan Chen, Xiaoli Hirayasu, Kouyuki Sun, Hanzi Lam, Yeeling Chen, Liping Wang, Qihui Song, Chun Huang, Niu Gao, George F. Jiang, Youxing Arase, Hisashi Zhang, Cheng Cheng |
| Affiliation | Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA. Peking Univ, Shenzhen Grad Sch, Sch Chem Biol & Biotechnol, Lab Chem Genom, Shenzhen, Peoples R China. Shanghai Jiao Tong Univ, Sch Med, Dept Pathophysiol,Shanghai Univ Inst Chem Biol E, Key Lab Cell Differentiat & Apoptosis Chinese,Min, Shanghai 200030, Peoples R China. Osaka Univ, Microbial Dis Res Inst, Dept Immunochem, Osaka, Japan. Osaka Univ, World Premier Int Immunol Frontier Res Ctr, Lab Immunochem, Osaka, Japan. Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Osaka, Japan. Natl Inst Biol Sci, Beijing, Peoples R China. Chinese Acad Sci, Inst Microbiol, Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China. Shandong Univ, Jinan 250100, Peoples R China. Natl New Drug R&D Ctr Shandong, Jinan, Peoples R China. Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA. Chongqing South Rd 280, Shanghai 200025, Peoples R China. |
| Keywords | HEMATOPOIETIC STEM-CELLS EX-VIVO EXPANSION UMBILICAL-CORD BLOOD PROGENITOR CELLS SELF-RENEWAL HLA-G TRANSPLANTATION PROTEINS RECEPTORS RECOGNITION |
| Issue Date | 2014 |
| Publisher | blood |
| Citation | BLOOD.2014,124,(6),924-935. |
| Abstract | A better understanding of the interaction between extrinsic factors and surface receptors on stem cells will greatly benefit stem cell research and applications. Recently, we showed that several angiopoietin-like proteins (Angptls) bind and activate the immune inhibitory receptor human leukocyte immunoglobulin(Ig)-like receptor B2(LILRB2) to support ex vivo expansion of hematopoietic stem cells (HSCs) and leukemia development. However, the molecular basis for the interaction between Angptls and LILRB2 was unclear. Here, we demonstrate that Angptl2 expressed in mammalian cells forms high-molecular-weight species and that lig and multimerization is required for activation of LILRB2 for downstream signaling. A novel motif in the first and fourth Ig domains of LILRB2 was identified that is necessary for the receptor to be bound and activated by Angptl2. The binding of Angptl2 to LILRB2 is more potent than and not completely overlapped with the binding of another ligand, HLA-G. Immobilized anti-LILRB2 antibodies induce a more potent activation of LILRB2 than Angptl2, and we developed a serum-free culture containing defined cytokines and immobilized anti-LILRB2 that supports a net expansion of repopulating human cord blood HSCs. Our elucidation of the mode of Angptl binding to LILRB2 enabled the development of a new approach for ex vivo expansion of human HSCs. |
| URI | http://hdl.handle.net/20.500.11897/342150 |
| ISSN | 0006-4971 |
| DOI | 10.1182/blood-2014-01-549162 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 化学生物学与生物技术学院 |
