The signal transduction pathway of CD23 (Fc epsilon RIIb) targets I kappa B kinase

Citation
Rm. Ten et al., The signal transduction pathway of CD23 (Fc epsilon RIIb) targets I kappa B kinase, J IMMUNOL, 163(7), 1999, pp. 3851-3857
Citations number
23
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
163
Issue
7
Year of publication
1999
Pages
3851 - 3857
Database
ISI
SICI code
0022-1767(19991001)163:7<3851:TSTPOC>2.0.ZU;2-8
Abstract
Alveolar macrophages play a crucial role in initiating the inflammatory res ponse in allergic asthma through the cross-linking of the low affinity IgE receptors (Fc epsilon RIIb or CD23) by IgE-allergen immunocomplexes. We hav e previously shown that CD23 cross-linking in monocytes and U937 cells targ ets I kappa B alpha, leading to the activation of the transcription factor NF-kappa B. We demonstrate in this paper that CD23-initiated signaling in U 937 cells leads to hyperphosphorylation of I kappa B alpha at Ser(32)/Ser(3 6) residues. Overexpression of a dominant-negative I kappa B alpha transgen e containing mutations at Ser(32)/Ser(36) completely inhibits degradation o f I kappa B alpha, NF-kappa B activation, and gene transcription that follo ws CD23 cross-linking. Investigation of the second messengers mediating the CD23-dependent activation of NF kappa B demonstrates that I kappa B kinase s (IKKs) but not p90(rsk) are selectively activated following CD23 cross-li nking and mediates the phosphorylation of I kappa B alpha. Cotransfection e xperiments with an IKK beta negative dominant completely inhibit CD23 induc ed NF kappa B activation. Furthermore, the activation of tyrosine kinase(s) by CD23 is required for the induction of IKK activity, I kappa B alpha deg radation, and NF-kappa B nuclear translocation. Taken together, our results show that CD23 cross-linking in the monocytic lineage induces tyrosine kin ase activation followed by activation of IKK, which phosphorylates I kappa B alpha at the N-terminal domain (Ser(32)/Ser(36)), inducing its degradatio n, NF-kappa B activation and gene transcription.