|
|
||||||||
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York, 14853
To investigate structural features critical for signal initiation by Ag-stimulated immunoreceptors, we constructed a series of single-chain chimeric receptors that incorporate extracellular human Fc
RI
for IgE binding, a variable transmembrane (TM) segment, and the ITAM-containing cytoplasmic tail of the TCR
-chain. We find that functional responses mediated by these receptors are strongly dependent on their TM sequences, and these responses are highly correlated to cross-link-dependent association with detergent-resistant lipid rafts. For one chimera designated
F
, mutation of a TM cysteine abolishes robust signaling and lipid raft association. In addition, TM disulfide-mediated oligomerization of another chimeric receptor, 

, enhances signaling. These results demonstrate an important role for TM segments in immunoreceptor signaling and a strong correspondence between strength of signaling and cross-link-dependent partitioning into ordered membrane domains.
This article has been cited by other articles:
![]() |
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] |
||||
![]() |
D. A. Brown Lipid Rafts, Detergent-Resistant Membranes, and Raft Targeting Signals. Physiology, December 1, 2006; 21(6): 430 - 439. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. R. Larson, J. A. Gosse, D. A. Holowka, B. A. Baird, and W. W. Webb Temporally resolved interactions between antigen-stimulated IgE receptors and Lyn kinase on living cells J. Cell Biol., November 7, 2005; 171(3): 527 - 536. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |