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Activation and regulation of the IκB kinase in human B cells by CD40 signaling

✍ Scribed by Yoko Kosaka; David M. Calderhead; Eric M. Manning; John E. Hambor; Amelia Black; Romas Geleziunas; Kenneth B. Marcu; Randolph J. Noelle

Publisher
John Wiley and Sons
Year
1999
Tongue
English
Weight
162 KB
Volume
29
Category
Article
ISSN
0014-2980

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✦ Synopsis

This study demonstrates that the engagement of CD40 results in the activation of the recently described I O B kinase (IKK) in a human B cell line. The kinase appears to reside within the cell in a cytosolic signalsome complex consisting of IKK, I O B, and an MKP-1-like molecule. While the binding of CD154 to CD40 induces the assembly of a CD40-TRAF receptor complex, IKK is not recruited to this complex. Nonetheless, a functional link between TRAF2 and IKK activity in B cells is demonstrated by the fact that overexpression of TRAF2 constitutively induces IKK activity, NF-O B luciferase and Fas expression. Synergy in the activation of IKK and NF-O B-dependent gene expression was observed by the simultaneous engagement of the B cell receptor and CD40, establishing an early means for crosstalk between these two B cell activation pathways. This study discusses the sequential biochemical events that transpire upon CD40 engagement by its ligand in human B cells.

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