Phosphorylation/dephosphorylation of high-affinity IgE receptors: a mechanism for coupling/uncoupling a large signaling complex.
Engagement of high-affinity IgE receptors leads to activation of tyrosine and serine/threonine kinases and the immediate phosphorylation of receptor beta (serine and tyrosine) and gamma (threonine and tyrosine) chains. Receptor disengagement leads to dephosphorylation of beta and gamma chains via the action of undefined phosphatases. Here we have identified five distinct polypeptides associated with the high-affinity IgE-receptor tetrameric complex, which apparently become phosphorylated and dephosphorylated in sequence with the beta and gamma chains. Like beta chain, polypeptides pp180, pp48, pp42, and pp28 are phosphorylated on serine and tyrosine, whereas pp125 is only phosphorylated on serine. The phosphorylation of each of these receptor-associated polypeptides is antigen-dose dependent and is restricted to activated receptor complexes. Furthermore the physical association between pp125 and the receptor is quantitatively affected by receptor phosphorylation and dephosphorylation, indicating a coupling-uncoupling mechanism. Finally, in vitro kinase experiments show that activated receptor complexes are also physically associated with tyrosine and serine/threonine kinases as part of a larger complex containing the phosphorylated polypeptides.
Paolini
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National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
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D000818:Animals; D003545:Cysteine / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D015151:Immunoblotting; D015471:Leukemia, Basophilic, Acute; D046911:Macromolecular Substances; D008715:Methionine / Q000378:metabolism; D008970:Molecular Weight; D010710:Phosphates / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D051381:Rats; D017455:Receptors, IgE / Q000302:isolation & purification / Q000378:metabolism*; D015398:Signal Transduction; D013462:Sulfur Radioisotopes; D014407:Tumor Cells, Cultured
D046911:Macromolecular Substances; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D017455:Receptors, IgE; D013462:Sulfur Radioisotopes; D008715:Methionine; D003545:Cysteine