Analysis of Proteins Binding to the ITAM Motif of the β-Subunit of the High-Affinity Receptor for IgE (Fc RI)

Aggregation of the multichain (α β γ2) high-affinity IgE receptor (Fc RI) initiates a signaling cascade that results in the release of allergic mediators. The cytoplasmic tails of the Fc RI-β and -γ subunits contain immunoreceptor tyrosine-based activation motifs (ITAMs). Phosphorylation of the γ IT...

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Bibliographic Details
Published in:Journal of receptors and signal transduction 2007, Vol.27 (1), p.67-81
Main Authors: SOTO-CRUZ, ISABEL, OLIVER, JANET M., ORTEGA, ENRIQUE
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Amino Acid Sequence
Animals
Cell Line
Fcε
Intracellular Signaling Peptides and Proteins - metabolism
ITAM
Molecular Sequence Data
Peptides - metabolism
Phosphorylation
Phosphotransferases - metabolism
Protein Binding
Protein-Tyrosine Kinases - metabolism
Rats
Receptors, IgE - genetics
Receptors, IgE - metabolism
Syk
Syk Kinase
Tyrosine - metabolism
Tyrosine phosphorylation
β-subunit
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Summary:Aggregation of the multichain (α β γ2) high-affinity IgE receptor (Fc RI) initiates a signaling cascade that results in the release of allergic mediators. The cytoplasmic tails of the Fc RI-β and -γ subunits contain immunoreceptor tyrosine-based activation motifs (ITAMs). Phosphorylation of the γ ITAM mediates activation of Syk kinase and is sufficient for triggering the responses induced by Fc RI crosslinking. Phosphorylation of the β ITAM is insufficient to mediate cell activation. The rat β ITAM contains three tyrosines (Tyr218, Tyr224, and Tyr228) with an intermediate noncanonical tyrosine. Synthetic peptides based on the ITAM of the Fc RI-β subunit were used to investigate the role of each phosphotyrosine in the binding of signaling proteins to this motif. Among the proteins that bind to phosphorylated β ITAM are Syk, Grb2, Shc, SHIP, and SHP-1, and binding does not depend on previous cell activation. Nonphosphorylated peptides do not bind these proteins. Syk binding to β -peptides is dependent on the number and position of phosphotyrosines in the ITAM. Phosphorylation of Tyr218 seems to be most important for Syk binding. Recruitment of Syk and other signaling proteins to the β -subunit might be important for its amplifier role.
ISSN:1079-9893
1532-4281
DOI:10.1080/10799890601096686