Zhong H, SuYang H, Erdjument-Bromage H, Tempst P, Ghosh S
Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Cell. 1997 May 2;89(3):413-24. doi: 10.1016/s0092-8674(00)80222-6.
Stimulation of cells with inducers of NF-kappaB such as LPS and IL-1 leads to the degradation of IkappaB-alpha and IkappaB-beta proteins and translocation of NF-kappaB to the nucleus. We now demonstrate that, besides the physical partitioning of inactive NF-kappaB to the cytosol, the transcriptional activity of NF-kappaB is regulated through phosphorylation of NF-kappaB p65 by protein kinase A (PKA). The catalytic subunit of PKA (PKAc) is maintained in an inactive state through association with IkappaB-alpha or IkappaB-beta in an NF-kappaB-IkappaB-PKAc complex. Signals that cause the degradation of IkappaB result in activation of PKAc in a cAMP-independent manner and the subsequent phosphorylation of p65. Therefore, this pathway represents a novel mechanism for the cAMP-independent activation of PKA and the regulation of NF-kappaB activity.
用脂多糖（LPS）和白细胞介素-1（IL-1）等核因子κB（NF-κB）诱导剂刺激细胞会导致IκB-α和IκB-β蛋白降解以及NF-κB易位至细胞核。我们现在证明，除了无活性的NF-κB在细胞质中的物理分隔外，NF-κB的转录活性还通过蛋白激酶A（PKA）对NF-κB p65的磷酸化来调节。PKA的催化亚基（PKAc）通过与NF-κB-IκB-PKAc复合物中的IκB-α或IκB-β结合而维持在无活性状态。导致IκB降解的信号以不依赖环磷酸腺苷（cAMP）的方式激活PKAc，并随后使p65磷酸化。因此，该途径代表了一种不依赖cAMP激活PKA以及调节NF-κB活性的新机制。
