PHOSPHORYLATION OF NF-KAPPA-B P65 BY PKA STIMULATES TRANSCRIPTIONAL ACTIVITY BY PROMOTING A NOVEL BIVALENT INTERACTION WITH THE COACTIVATORCBP P300/

The transcriptional activity of NF-kappa B is stimulated upon phosphor ylation of its p65 subunit on serine 276 by protein kinase A (PKA). Th e transcriptional coactivator CBP/p300 associates with NF-kappa B p65 through two sites, an N-terminal domain that interacts with the C-term inal region of unphosphorylated p65, and a second domain that only int eracts with p65 phosphorylated on serine 276. Accessibility to both si tes is blocked in unphosphorylated p65 through an intramolecular maski ng of the N terminus by the C-terminal region of pS5. Phosphorylation by PKA both weakens the interaction between the N- and C-terminal regi ons of p65 and creates an additional site for interaction with CBP/p30 0. Therefore, PKA regulates the transcriptional activity of NF-kappa B by modulating its interaction with CBP/p300.