Department of Laboratory Medicine and Pathology, Center for Immunology, Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
J Biol Chem. 2010 Apr 9;285(15):11100-5. doi: 10.1074/jbc.M109.068999. Epub 2010 Feb 17.
NF-kappaB activation following engagement of the antigen-specific T cell receptor involves protein kinase C-theta-dependent assembly of the CARMA1-BCL10-MALT1 (CBM) signalosome, which coordinates downstream activation of IkappaB kinase (IKK). We previously identified a novel role for the adhesion- and degranulation-promoting adapter protein (ADAP) in regulating the assembly of the CBM complex via an interaction of ADAP with CARMA1. In this study, we identify a novel site in ADAP that is critical for association with the TAK1 kinase. ADAP is critical for recruitment of TAK1 and the CBM complex, but not IKK, to protein kinase C-theta. ADAP is not required for TAK1 activation. Although both the TAK1 and the CARMA1 binding sites in ADAP are essential for IkappaB alpha phosphorylation and degradation and NF-kappaB nuclear translocation, only the TAK1 binding site in ADAP is necessary for IKK phosphorylation. In contrast, only the CARMA1 binding site in ADAP is required for ubiquitination of IKKgamma. Thus, distinct sites within ADAP control two key activation responses that are required for NF-kappaB activation in T cells.
NF-κB 的激活后，从事抗原特异性 T 细胞受体涉及蛋白激酶 C-θ-依赖组装的 CARMA1-BCL10-MALT1（CBM）信号体，协调下游激活的 IkappaB 激酶（IKK）。我们以前确定了一个新的作用的粘附和脱颗粒促进适配器蛋白（ADAP）在调节组装的 CBM 复合物通过相互作用的 ADAP 与 CARMA1。在这项研究中，我们确定了一个新的网站，在 ADAP 是至关重要的协会与 TAK1 激酶。ADAP 是至关重要的招募 TAK1 和 CBM 复合物，但不是 IKK，蛋白激酶 C-θ。ADAP 不需要 TAK1 激活。虽然这两个 TAK1 和 CARMA1 结合位点在 ADAP 是必不可少的 IkappaB α磷酸化和降解和 NF-κB 核易位，只有 TAK1 结合位点在 ADAP 是必需的 IKK 磷酸化。相比之下，只有 CARMA1 结合位点在 ADAP 是必需的泛素化的 IKKγ。因此，不同的网站内 ADAP 控制两个关键的激活反应，这是必需的 NF-κB 激活的 T 细胞。
