|
|
||||||||
R Signaling1


* Department of Allergy and Rheumatology, Graduate School of Medicine and Faculty of Medicine, and
Department of Oncology, Institute of Medical Science, University of Tokyo, Tokyo, Japan;
Department of Oncogene Research, Research Institute for Microbial Disease, Osaka University, Osaka, Japan
Characterization of lipid rafts as separated membrane microdomains
consist of heterogeneous proteins suggesting that lateral assembly of
rafts after Ag receptor cross-linking represents the earliest signal
generating process. In line with the concept, cross-linked Ag receptors
have been shown to associate with detergent-insoluble raft fraction
without the aid of Src family kinases. However, it has not been
established whether spatial raft coalescence could also precede Src
family kinase activation. In this study, we showed that spatial raft
coalescence after low-affinity Fc
R cross-linking in RAW264.7
macrophages is independent of Src family kinase activity. The lateral
raft assembly was found to be ascribed to the action of ligand-binding
subunits, rather than to immunoreceptor tyrosine-based activation
motif-bearing signal subunits, because monomeric murine Fc
RIIb
expressed in rat basophilic leukemia cells successfully induced spatial
raft reorganization after cross-linking. We also showed that
extracellular and transmembrane region of Fc
RIIb is sufficient for
raft stabilization. Moreover, this receptor fragment triggers rapid
calcium mobilization and linker for activation of T cells
phosphorylation, in a manner sensitive to Src family kinase inhibition
and to cholesterol depletion. Presence of immunoreceptor tyrosine-based
inhibitory motif and addition of immunoreceptor tyrosine-based
activation motif to the receptor fragment abolished and enhanced the
responses, respectively, but did not affect raft stabilization. These
findings support the concept that ligand-binding subunit is responsible
for raft coalescence, and that this event triggers initial biochemical
signaling.
This article has been cited by other articles:
![]() |
C. H. Serezani, D. M. Aronoff, R. G. Sitrin, and M. Peters-Golden Fc{gamma}RI ligation leads to a complex with BLT1 in lipid rafts that enhances rat lung macrophage antimicrobial functions Blood, October 8, 2009; 114(15): 3316 - 3324. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Serre-Beinier, D. Bosco, L. Zulianello, A. Charollais, D. Caille, E. Charpantier, B. R. Gauthier, G. R. Diaferia, B. N. Giepmans, R. Lupi, et al. Cx36 makes channels coupling human pancreatic {beta}-cells, and correlates with insulin expression Hum. Mol. Genet., February 1, 2009; 18(3): 428 - 439. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. K. Huynh, E. Gershenzon, and S. Grinstein Cholesterol Accumulation by Macrophages Impairs Phagosome Maturation J. Biol. Chem., December 19, 2008; 283(51): 35745 - 35755. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. V. Kondadasula, J. M. Roda, R. Parihar, J. Yu, A. Lehman, M. A. Caligiuri, S. Tridandapani, R. W. Burry, and W. E. Carson III Colocalization of the IL-12 receptor and Fc{gamma}RIIIa to natural killer cell lipid rafts leads to activation of ERK and enhanced production of interferon-{gamma} Blood, April 15, 2008; 111(8): 4173 - 4183. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. W. Sohn, S. K. Pierce, and S.-J. Tzeng Live Cell Imaging Reveals that the Inhibitory Fc{gamma}RIIB Destabilizes B Cell Receptor Membrane-Lipid Interactions and Blocks Immune Synapse Formation J. Immunol., January 15, 2008; 180(2): 793 - 799. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. T. T. Nguyen, L. Charrier-Hisamuddin, G. Dalmasso, A. Hiol, S. Sitaraman, and D. Merlin Association of PepT1 with lipid rafts differently modulates its transport activity in polarized and nonpolarized cells Am J Physiol Gastrointest Liver Physiol, December 1, 2007; 293(6): G1155 - G1165. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Garcia-Garcia, E. J. Brown, and C. Rosales Transmembrane Mutations to Fc{gamma}RIIA Alter Its Association with Lipid Rafts: Implications for Receptor Signaling J. Immunol., March 1, 2007; 178(5): 3048 - 3058. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Szabo, A. Dolganiuc, Q. Dai, and S. B. Pruett TLR4, Ethanol, and Lipid Rafts: A New Mechanism of Ethanol Action with Implications for other Receptor-Mediated Effects J. Immunol., February 1, 2007; 178(3): 1243 - 1249. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Kono, C. Kyogoku, T. Suzuki, N. Tsuchiya, H. Honda, K. Yamamoto, K. Tokunaga, and Z.-I. Honda Fc{gamma}RIIB Ile232Thr transmembrane polymorphism associated with human systemic lupus erythematosus decreases affinity to lipid rafts and attenuates inhibitory effects on B cell receptor signaling Hum. Mol. Genet., October 1, 2005; 14(19): 2881 - 2892. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Mina-Osorio and E. Ortega Aminopeptidase N (CD13) functionally interacts with Fc{gamma}Rs in human monocytes J. Leukoc. Biol., June 1, 2005; 77(6): 1008 - 1017. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Lesourne, W. H. Fridman, and M. Daeron Dynamic Interactions of Fc{gamma} Receptor IIB with Filamin-Bound SHIP1 Amplify Filamentous Actin-Dependent Negative Regulation of Fc{epsilon} Receptor I Signaling J. Immunol., February 1, 2005; 174(3): 1365 - 1373. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. A. Swanson and A. D. Hoppe The coordination of signaling during Fc receptor-mediated phagocytosis J. Leukoc. Biol., December 1, 2004; 76(6): 1093 - 1103. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. L. W. Hazenbos, B. E. Clausen, J. Takeda, and T. Kinoshita GPI-anchor deficiency in myeloid cells causes impaired Fc{gamma}R effector functions Blood, November 1, 2004; 104(9): 2825 - 2831. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |