tailieunhanh - Báo cáo khoa học: Identification of functional domains in the formyl peptide receptor-like 1 for agonist-induced cell chemotaxis

Formyl peptide receptor-like 1 (FPRL1) is a seven transmembrane domain, G protein-coupled receptor that interacts with a variety of exogenous and host-derived agonists. In order to identify domains crucial for ligand recog-nition by FPRL1, we used chimeric receptors with segments in FPRL1 replaced by corresponding amino acid sequences derived from the proto-type formyl peptide receptor FPR. The chimeric receptors were stably transfected into human embryonic kidney epithelial cells and the capacity of the cells to migrate in response to formyl peptide receptor agonists was evaluated. . | ềFEBS Journal Identification of functional domains in the formyl peptide receptor-like 1 for agonist-induced cell chemotaxis Yingying Le1 2 Richard D. Ye3 Wanghua Gong4 Jianxiang Li1 Pablo Iribarren1 and Ji Ming Wang1 1 Laboratory of Molecular Immunoregulation Center for Cancer Research NationalCancer Institute at Frederick MD USA 2 Institute for NutritionalSciences Shanghai Institutes for BiologicalSciences Chinese Academy of Sciences Shanghai China 3 Department of Pharmacology College of Medicine University of Illinois at Chicago IL USA 4 Basic Research Program Center for Cancer Research NationalCancer Institute at Frederick MD USA Keywords chemotaxis formyl peptide receptor formyl peptide receptor-like 1 structure-function Correspondence J M Wang LMI CCR NCI-Frederick Bldg. 560 Rm 31-40 Frederick MD 21702 USA E-mail wangji@ Received 19 August 2004 revised 23 November 2004 accepted 3 December 2004 doi Formyl peptide receptor-like 1 FPRL1 is a seven transmembrane domain G protein-coupled receptor that interacts with a variety of exogenous and host-derived agonists. In order to identify domains crucial for ligand recognition by FPRL1 we used chimeric receptors with segments in FPRL1 replaced by corresponding amino acid sequences derived from the prototype formyl peptide receptor FPR. The chimeric receptors were stably transfected into human embryonic kidney epithelial cells and the capacity of the cells to migrate in response to formyl peptide receptor agonists was evaluated. Our results showed that multiple domains in FPRL1 are involved in the receptor response to chemotactic agonists with the sixth transmembrane domain and the third extracellular loop playing a prominent role. Interestingly the N-terminus and a segment between the fourth transmembrane domain and the third intracellular loop of FPRL1 are important for receptor interaction with a 42 amino acid amyloid b peptide Ab42 an Alzheimer s disease-associated