PMID- 17498065
OWN - NLM
STAT- MEDLINE
DCOM- 20070716
LR  - 20071203
IS  - 0105-2896 (Print)
IS  - 0105-2896 (Linking)
VI  - 217
DP  - 2007 Jun
TI  - Insights into immunoglobulin E receptor signaling from structurally defined 
      ligands.
PG  - 269-79
AB  - The asymmetrical structure of bent immunoglobulin E (IgE) bound to its 
      high-affinity receptor, Fc epsilon RI, suggests a possible role for this 
      configuration in the regulation of signaling mediated by cross-linking of Fc 
      epsilon RI on the surface of mast cells and basophils. Indeed, the presence of 
      bound IgE strongly influences the capacity of cross-linked Fc epsilon RI dimers 
      to trigger mast cell degranulation, implicating orientational constraints by 
      bound IgE. Bivalent ligands that cross-link by binding to bivalent IgE can form 
      linear and cyclic chains of IgE/Fc epsilon RI complexes, and these exhibit only 
      limited capacity to stimulate downstream signaling and degranulation, whereas 
      structurally analogous trivalent ligands, which can form branched networks of 
      cross-linked IgE/Fc epsilon RI complexes, are more effective at cell activation. 
      Long bivalent ligands with flexible spacers can form intramolecular cross-links 
      with IgE, and these stable 1:1 complexes are very potent inhibitors of mast cell 
      degranulation stimulated by multivalent antigen. In contrast, trivalent ligands 
      with rigid double-stranded DNA spacers effectively stimulate degranulation 
      responses in a length-dependent manner, providing direct evidence for receptor 
      transphosphorylation as a key step in the mechanism of signaling by Fc epsilon 
      RI. Thus, studies with chemically defined oligovalent ligands show important 
      features of IgE receptor cross-linking that regulate signaling, leading to mast 
      cell activation.
FAU - Holowka, David
AU  - Holowka D
AD  - Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 
      14853-1301, USA. dah24@cornell.edu
FAU - Sil, Dwaipayan
AU  - Sil D
FAU - Torigoe, Chikako
AU  - Torigoe C
FAU - Baird, Barbara
AU  - Baird B
LA  - eng
GR  - AI22449/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
PL  - England
TA  - Immunol Rev
JT  - Immunological reviews
JID - 7702118
RN  - 0 (Ligands)
RN  - 0 (Receptors, IgE)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - DNA/chemistry/immunology
MH  - Humans
MH  - Immunoglobulin E/*immunology
MH  - Ligands
MH  - Receptors, IgE/antagonists & inhibitors/*chemistry/*immunology
MH  - Signal Transduction
RF  - 63
EDAT- 2007/05/15 09:00
MHDA- 2007/07/17 09:00
CRDT- 2007/05/15 09:00
PHST- 2007/05/15 09:00 [pubmed]
PHST- 2007/07/17 09:00 [medline]
PHST- 2007/05/15 09:00 [entrez]
AID - IMR517 [pii]
AID - 10.1111/j.1600-065X.2007.00517.x [doi]
PST - ppublish
SO  - Immunol Rev. 2007 Jun;217:269-79. doi: 10.1111/j.1600-065X.2007.00517.x.