Activation and regulation of the IkappaB kinase in human B cells by CD40 signaling.
This study demonstrates that the engagement of CD40 results in the activation of the recently described IkappaB kinase (IKK) in a human B cell line. The kinase appears to reside within the cell in a cytosolic signalsome complex consisting of IKK, IkappaB, 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-kappaB luciferase and Fas expression. Synergy in the activation of IKK and NF-kappaB-dependent gene expression was observed by the simultaneous engagement of the B cell receptor and CD40, establishing an early means for cross-talk 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.
Kosaka
Y
Y
Graduate Program in Molecular and Cellular Biology, Dartmouth Medical School, Lebanon, NH 03756, USA.
Calderhead
D M
DM
Manning
E M
EM
Hambor
J E
JE
Black
A
A
Geleziunas
R
R
Marcu
K B
KB
Noelle
R J
RJ
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology*; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand; D004789:Enzyme Activation; D006801:Humans; D051550:I-kappa B Kinase; D008562:Membrane Glycoproteins / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011506:Proteins / Q000502:physiology; D011817:Rabbits; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D047992:TNF Receptor-Associated Factor 2; D014407:Tumor Cells, Cultured
D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D011506:Proteins; D011947:Receptors, Antigen, B-Cell; D047992:TNF Receptor-Associated Factor 2; D023201:CD40 Ligand; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human