蛋白激酶A对核因子-κB p65的磷酸化通过促进与共激活因子CBP/p300的新型二价相互作用来刺激转录活性。
Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300.
作者信息
Zhong H, Voll R E, Ghosh S
机构信息
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
出版信息
Mol Cell. 1998 Apr;1(5):661-71. doi: 10.1016/s1097-2765(00)80066-0.
The transcriptional activity of NF-kappa B is stimulated upon phosphorylation of its p65 subunit on serine 276 by protein kinase A (PKA). The transcriptional coactivator CPB/p300 associates with NF-kappa B p65 through two sites, an N-terminal domain that interacts with the C-terminal region of unphosphorylated p65, and a second domain that only interacts with p65 phosphorylated on serine 276. Accessibility to both sites is blocked in unphosphorylated p65 through an intramolecular masking of the N terminus by the C-terminal region of p65. Phosphorylation by PKA both weakens the interaction between the N- and C-terminal regions of p65 and creates an additional site for interaction with CBP/p300. Therefore, PKA regulates the transcriptional activity of NF-kappa B by modulating its interaction with CBP/p300.
蛋白激酶A（PKA）使核因子-κB（NF-κB）的p65亚基的丝氨酸276磷酸化后，NF-κB的转录活性受到刺激。转录共激活因子CPB/p300通过两个位点与NF-κB p65结合，一个是与未磷酸化p65的C末端区域相互作用的N末端结构域，另一个是仅与丝氨酸276磷酸化的p65相互作用的第二个结构域。在未磷酸化的p65中，通过p65的C末端区域对N末端的分子内掩盖，这两个位点的可及性均被阻断。PKA介导的磷酸化既减弱了p65的N末端和C末端区域之间的相互作用，又为与CBP/p300的相互作用创造了一个额外的位点。因此，PKA通过调节NF-κB与CBP/p300的相互作用来调控NF-κB的转录活性。
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