p28, a novel IgE receptor-associated protein, is a sensor of receptor occupation by its ligand in mast cells.
Mast cells express the high affinity receptor for IgE (FcepsilonRI). Aggregation of this receptor by IgE and antigen leads to a signaling cascade resulting in the secretion of histamine, in the synthesis of other pro-inflammatory mediators such as leukotrienes and prostaglandins, and in the production of various cytokines, all of which participate in the development of the allergic reaction. In the last years, growing evidence accumulated that binding of IgEs to FcepsilonRI in itself induces active signals leading to mast cell survival, increased expression of FcepsilonRI, transient induction of histidine decarboxylase synthesis, and increased cell adhesion. The mechanisms underlying monomeric IgE signaling in the absence of receptor aggregation are still poorly understood. Here, we show that a protein of 28 kDa (p28) is physically and constitutively associated with FcepsilonRI in mast cells. Coimmunoprecipitation studies from (125)I surface-labeled cells demonstrated that this association involves at least 50% of membrane-expressed FcepsilonRI. After the addition of monomeric IgE to the cells, the p28.FcepsilonRI complex dissociates almost completely in less than 2 min. This dissociation is temperature-sensitive and is not due to the recruitment of additional proteins to the complex. Stripping bound IgE from the cells by acidic treatment promotes a rapid reassociation between p28 and FcepsilonRI. Altogether, these data are consistent with a conformational regulation of the complex. Thus, p28 is a sensor for FcepsilonRI occupation by IgE on mast cells, and its dissociation from the receptor could represent an early step of monomeric IgE signaling.
Charles
Nicolas
N
INSERM EMI-0225, Faculté de Médecine Xavier Bichat, 16 rue Henri Huchard, 75870 Paris Cedex 18, France.
Monteiro
Renato C
RC
Benhamou
Marc
M
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002352:Carrier Proteins / Q000737:chemistry* / Q000502:physiology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D006640:Histidine Decarboxylase / Q000378:metabolism; D015151:Immunoblotting; D007073:Immunoglobulin E / Q000737:chemistry; D007455:Iodine / Q000494:pharmacology; D008024:Ligands; D008407:Mast Cells / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D017455:Receptors, IgE / Q000737:chemistry*; D015398:Signal Transduction; D013696:Temperature; D013997:Time Factors
D002352:Carrier Proteins; D008024:Ligands; D017455:Receptors, IgE; D007073:Immunoglobulin E; D007455:Iodine; D006640:Histidine Decarboxylase