We have generated a monoclonal directed against the alpha chain of the human FcepsilonRI. With this reagent we found that FcepsilonRI is expressed on the surface of Langerhans cells in human skin and we are attempting to determine the possible role of this receptor in atopic dermatitis. We are also looking actively at the possibility that FcepsilonRI might be expressed in other cells such as eosinophils, macrophages, NK cells etc... Z01AI00665 The high affinity IgE receptor belongs to a class of receptors which lack intrinsic kinase activity, but activates non-receptor tyrosine and serine / threonine kinases. Receptor engagement triggers a chain of signalling events leading from protein phosphorylation to activation of phosphotidylinositol-specific phospholipase C, an increase in intracellular calcium levels, and ultimately the activation of more specialized functions. We have investigated the role of the ~ and gamma chains in signal transduction. We found (1) that receptor engagement induces immediate phosphorylation of beta (tyrosine and serine) and of gamma (tyrosine and threonine); (2) that this phosphorylation is specific to activated receptors and is reversible upon receptor disengagement; (3) that the gamma chains are critical for signal transduction but that the ~ chain does not seem necessary; (4) that phosphorylation / dephosphorylation is a coupling / uncoupling mechanism; (5) that the receptor activates two distinct phosphorylation pathways, one cell- specific and the other not. We are at present trying to identify the role of beta and are studying further the role of receptor phosphorylation in cell activation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000664-01
Application #
3790897
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code