| Title | Cyclophilin A (CyPA) Induces Chemotaxis Independent of Its Peptidylprolyl Cis-Trans Isomerase Activity DIRECT BINDING BETWEEN CyPA AND THE ECTODOMAIN OF CD147 |
| Authors | Song, Fei Zhang, Xin Ren, Xiao-Bai Zhu, Ping Xu, Jing Wang, Li Li, Yi-Fei Zhong, Nan Ru, Qiang Zhang, Da-Wei Jiang, Jian-Li Xia, Bin Chen, Zhi-Nan |
| Affiliation | Peking Univ, Beijing Nucl Magnet Resonance Ctr, Beijing 100871, Peoples R China. Peking Univ, Coll Chem & Mol Engn, Beijing 100871, Peoples R China. Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China. Fourth Mil Med Univ, Xijing Hosp, Dept Clin Immunol, Xian 710032, Peoples R China. Fourth Mil Med Univ, Xijing Hosp, Cell Engn Res Ctr, Xian 710032, Peoples R China. Fourth Mil Med Univ, Xijing Hosp, Dept Cell Biol, State Key Lab Canc Biol, Xian 710032, Peoples R China. |
| Keywords | CYCLOSPORINE-A BINDING SIGNAL-TRANSDUCTION CD147 ISOMERIZATION CANCER CATALYSIS PROTEIN CELLS IDENTIFICATION HAB18G/CD147 |
| Issue Date | 2011 |
| Publisher | journal of biological chemistry |
| Citation | JOURNAL OF BIOLOGICAL CHEMISTRY.2011,286,(10),8197-8203. |
| Abstract | Cyclophilin A (CyPA) is a ubiquitously distributed peptidylprolyl cis-transisomerase (PPIase) that possesses diverse biological functions. Extracellular CyPA is a potent chemokine, which can directly induce leukocyte chemotaxis and contribute to the pathogenesis of inflammation-mediated diseases. Although it has been identified that the chemotaxis activity of CyPA is mediated through its cell surface signaling receptor CD147, the role of CyPA PPIase activity in this process is disputable, and the underlying molecular mechanism is still poorly understood. In this study, we present the first evidence that CyPA induces leukocyte chemotaxis through a direct binding with the ectodomain of CD147 (CD147(ECT)), independent of its PPIase activity. Although NMR study indicates that the CD147(ECT) binding site on CyPA overlaps with the PPIase active site, the PPIase inactive mutant CyPA(R55A) exhibits similar CD147(ECT) binding ability and chemotaxis activity to those of CyPAWT. Furthermore, we have identified three key residues of CyPA involved in CD147(ECT) binding and found that mutations H70A, T107A, and R69A result in similar levels of reduction in CD147(ECT) binding ability and chemotaxis activity for CyPA, without affecting the PPIase activity. Our findings indicate that there exists a novel mechanism for CyPA to regulate cellular signaling processes, shedding new light on its applications in drug development and providing a new targeting site for drug design. |
| URI | http://hdl.handle.net/20.500.11897/394991 |
| ISSN | 0021-9258 |
| DOI | 10.1074/jbc.C110.181347 |
| Indexed | SCI(E) EI |
| Appears in Collections: | å å¦ä¸ å å å·¥ç¨ å¦é ¢ 生命科学学院 |
