Deciphering the pathway from the TCR to NF-kappaB.
A major regulator of lymphocyte survival and activation is the transcription factor nuclear factor-kappaB (NF-kappaB). Controlled activation of NF-kappaB is essential for the immune and inflammatory response as well as for cell proliferation and protection against apoptosis. The NEMO/IkappaB kinase (IKK) complex is the central integrator of most stimuli leading to NF-kappaB activation, but a detailed knowledge of the upstream events is available only for a limited number of stimuli. In particular, although most players have probably been identified, relatively little is known about the detailed molecular mechanisms involved in the cascade leading to NF-kappaB activation following engagement of the T-cell receptor by a foreign antigen. In this review, we discuss recent insights into this specific signal transduction cascade, and the way it is controlled both spatially and temporally.
Weil
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R
Unité de Signalisation Moléculaire et Activation Cellulaire, URA 2582 Centre National de la Recherche Scientifique, Institut Pasteur, 25 Rue du Dr. Roux, 75724 Paris Cedex 15, France.
Israël
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A
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D018442:Lymphoma, B-Cell, Marginal Zone / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D051550:I-kappa B Kinase; D011493:Protein Kinase C