| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Cell Biology and Physiology, University of New Mexico Health Science Center, Albuquerque, NM 87131
One of the major functions of the N-formyl peptide
receptor (FPR) is to mediate leukocyte degranulation. Phosphorylation
of the C-terminal domain of the FPR is required for receptor
internalization and desensitization. Although arrestins mediate
phosphorylation-dependent desensitization, internalization, and
initiation of novel signaling cascades for a number of G
protein-coupled receptors, their roles in FPR regulation and signaling
remain unclear. CXCR1-mediated degranulation of RBL-2H3 cells is
promoted by arrestin binding. To determine whether receptor
phosphorylation or arrestin binding is required to promote FPR-mediated
degranulation, we used RBL-2H3 cells stably transfected with either the
wild-type FPR or a mutant form, 
ST, which is incapable of undergoing
ligand-stimulated phosphorylation. We observed that stimulation of
wild-type FPR resulted in very low levels of degranulation compared
with that mediated by cross-linking of the Fc
RI receptor.
Stimulation of the ST mutant, however, resulted in levels of
degranulation comparable to those of the FcRI receptor,
demonstrating that neither receptor phosphorylation nor arrestin
binding was necessary to initiate FPR-mediated degranulation.
Degranulation initiated by the ST mutant was proportional to the
level of active cell surface receptor, suggesting that either receptor
internalization or desensitization may be responsible for terminating
degranulation of the wild-type FPR. To distinguish between these
possibilities, we used a partially phosphorylation-deficient mutant of
the FPR that can undergo internalization, but not desensitization.
Degranulation by this mutant FPR was indistinguishable from that of the
ST mutant, indicating that FPR phosphorylation or binding of
arrestin but not internalization terminates the degranulation
response.
This article has been cited by other articles:
|
|
 |
|
  E. J. Swindle, J. W. Coleman, F. R. DeLeo, and D. D. Metcalfe Fc{epsilon}RI- and Fc{gamma} Receptor-Mediated Production of Reactive Oxygen Species by Mast Cells Is Lipoxygenase- and Cyclooxygenase-Dependent and NADPH Oxidase-Independent J. Immunol., November 15, 2007; 179(10): 7059 - 7071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Xue, G. Hsieh, M. A. Raymond-Stintz, J. Pfeiffer, D. Roberts, S. L. Steinberg, J. M. Oliver, E. R. Prossnitz, D. S. Lidke, and B. S. Wilson Activated N-Formyl Peptide Receptor and High-Affinity IgE Receptor Occupy Common Domains for Signaling and Internalization Mol. Biol. Cell, April 1, 2007; 18(4): 1410 - 1420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Gaudreault, C. Thompson, J. Stankova, and M. Rola-Pleszczynski Involvement of BLT1 Endocytosis and Yes Kinase Activation in Leukotriene B4-Induced Neutrophil Degranulation J. Immunol., March 15, 2005; 174(6): 3617 - 3625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. R. Jala, W.-H. Shao, and B. Haribabu Phosphorylation-independent {beta}-Arrestin Translocation and Internalization of Leukotriene B4 Receptors J. Biol. Chem., February 11, 2005; 280(6): 4880 - 4887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Xue, C. M. Vines, T. Buranda, D. F. Cimino, T. A. Bennett, and E. R. Prossnitz N-Formyl Peptide Receptors Cluster in an Active Raft-associated State Prior to Phosphorylation J. Biol. Chem., October 22, 2004; 279(43): 45175 - 45184. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
