Receptor up-regulation, internalization, and interconverting receptor states - Critical components of a quantitative description of N-formyl peptide-receptor dynamics in the neutrophil

被引:46
作者
Hoffman, JF
Linderman, JJ
Omann, GM
机构
[1] VET ADM MED CTR, RES SERV 151, ANN ARBOR, MI 48105 USA
[2] UNIV MICHIGAN, DEPT CHEM ENGN, ANN ARBOR, MI 48109 USA
[3] UNIV MICHIGAN, SCH MED, DEPT BIOL CHEM, ANN ARBOR, MI 48105 USA
[4] UNIV MICHIGAN, SCH MED, DEPT SURG, ANN ARBOR, MI 48105 USA
关键词
D O I
10.1074/jbc.271.31.18394
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
High resolution kinetic data of the binding of fluorescent peptide to the N-formyl peptide receptor of neutrophils at 37 degrees C has allowed for the development of a ligand binding model that predicts statistically larger binding rate constants than those previously reported for intact neutrophils. The new model accounts for ligand association and dissociation, receptor up-regulation, ligand-receptor complex internalization, a change in receptor affinity, and the quenching of internalized fluorescent ligand. We determined that receptor up-regulation is both agonist- and temperature-induced and is inhibited by both phenylarsine oxide and pertussis toxin treatment. Model fits of ligand association to pertussis toxin-treated cells show that while receptor upregulation was inhibited, rate constants for ligand binding, receptor affinity conversion, and internalization of ligand-receptor complexes were unaffected. Results suggest G(1)-protein mediated receptor up-regulation and G(1)-protein-independent receptor affinity conversion, Simulation of ligand infusion using our model gives insight into the quantitative and dynamic relationship between the low affinity ligand-receptor complex and the actin polymerization response.
引用
收藏
页码:18394 / 18404
页数:11
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