Phosphorylation and dephosphorylation of the high-affinity receptor for immunoglobulin E immediately after receptor engagement and disengagement

TRIGGERING of mast cells and basophils by immunoglobulin E (IgE) and antigen induces various biochemical signals, including tyrosine kinase activation 1,2 , which lead to cell degranulation and the release of mediators of the allergic reaction. The high-affinity receptor for IgE (FcσRI) responsible for initiating these events is a complex structure composed of an IgE-binding α-chain, a β-chain and a homodimer of γ-chains 3 . It has been assumed that β and γ, which have extensive cytoplasmic domains, play an important but undefined role in coupling FcσRI to signal transduction mechanisms. Here we show that FcσRI engagement induces immediate in vivo phosphorylation on β(tyrosine and serine) and γ (tyrosine and threonine) by at least two different non-receptor kinases. We take advantage of unique features of this receptor system to demonstrate that the phosphorylation signal is restricted to activated receptors and is immediately reversible upon receptor disengagement by undefined phosphatases. Rapid phosphorylation and dephosphorylation may be a general mechanism to couple and uncouple activated receptors to other effector molecules. This could be particularly relevant to other multimeric receptors containing Fcσ RI γ-chains or the related ζ and η chains such as the T-cell antigen receptor (TCR) 4–6 and the low-affinity receptor for immunoglobulin G (FcγRIII, CD16) (refs 7–11).