AGONIST-INDUCED SEQUESTRATION, RECYCLING, AND RESENSITIZATION OF PLATELET-ACTIVATING-FACTOR RECEPTOR - ROLE OF CYTOPLASMIC TAIL PHOSPHORYLATION IN EACH PROCESS
I. Ishii et al., AGONIST-INDUCED SEQUESTRATION, RECYCLING, AND RESENSITIZATION OF PLATELET-ACTIVATING-FACTOR RECEPTOR - ROLE OF CYTOPLASMIC TAIL PHOSPHORYLATION IN EACH PROCESS, The Journal of biological chemistry, 273(16), 1998, pp. 9878-9885
Agonist-induced sequestration, recycling, and resensitization of plate
let-activating factor (PAF) receptor were characterized in transfected
Chinese hamster ovary cells. Exposure of the cells to PAF led to rapi
d sequestration of the receptors into the intracellular compartment an
d desensitization of the response to PAF, The sequestration was inhibi
ted by pretreatments that perturbed the clathrin-mediated pathway. Sub
sequent removal of PAF by washing with receptor antagonists led to rap
id recycling of the sequestered receptors to the cell surface accompan
ied by resensitization to PAF, To evaluate the potential role of phosp
horylation in the receptor cytoplasmic tail during these processes, mu
tant receptors in which the tails were truncated or substituted, so as
to lack serine/threonine residues, were created. PAF phosphorylated t
he wildtype receptor rapidly and strongly, but the mutants did not. Th
e maximal extent of sequestration of each mutant was lower than that o
f the wild-type, and one of the substituted mutants showed no sequestr
ation. Furthermore, the sequestration-defective mutant showed evidence
of desensitization after agonist stimulation but not resensitization
after agonist removal, Thus, agonist-induced phosphorylation of the cy
toplasmic tail facilitates but is not essential for receptor sequestra
tion, and sequestration/recycling appears important in receptor resens
itization.