Reactome | Protein kinase A (PKA) and RPS6KA5 (MSK1) phosphorylates p65 (RELA) subunit

Protein kinase A (PKA) and RPS6KA5 (MSK1) phosphorylates p65 (RELA) subunit

Stable Identifier

R-HSA-5624473

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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Protein kinase A (PKA) and RPS6KA5 (MSK1) phosphorylates p65 (RELA) subunit

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Protein kinase A (PKA/PRKACA) and Ribosomal protein S6 kinase alpha-5 (RPS6KA5/MSK1/SAPK1) phosphorylate serine 276 (S276) in the Rel homology domain (RHD) of nuclear p65 subunit RELA (Yoon et al. 2008, Reber et al. 2009). Few other phosphorylation sites (S311, S529 and S536) have also been proposed in RELA (Duran et al. 2003) note: in this reaction we are showing only S276 phosphorylation)). Phosphorylation of RELA subunit enhances the association of RELA with p300 and this is a prerequisite for later NF-kB modification by histone acetyltransferases (HATs) p300/CBP. Phosphorylation of RELA also cross-regulates CLEC7A (dectin-1) mediated non-canonical NF-kB pathway by forming inactive p65 and RELB dimers, that cannot bind DNA.

Literature References

PubMed ID	Title	Journal	Year
19122653	Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-kappaB activation through Raf-1 and Syk Gringhuis, SI, den Dunnen, J, Litjens, M, van der Vlist, M, Wevers, B, Bruijns, SC, Geijtenbeek, TB	Nat. Immunol.	2009
18385332	Protein kinase A-induced phosphorylation of the p65 subunit of nuclear factor-kappaB promotes Schwann cell differentiation into a myelinating phenotype Yoon, C, Korade, Z, Carter, BD	J. Neurosci.	2008
19197368	Ser276 phosphorylation of NF-kB p65 by MSK1 controls SCF expression in inflammation Reber, L, Vermeulen, L, Haegeman, G, Frossard, N	PLoS ONE	2009
12628924	Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1) Vermeulen, L, De Wilde, G, Van Damme, P, Vanden Berghe, W, Haegeman, G	EMBO J.	2003
17462920	C-type lectin DC-SIGN modulates Toll-like receptor signaling via Raf-1 kinase-dependent acetylation of transcription factor NF-kappaB Gringhuis, SI, den Dunnen, J, Litjens, M, van Het Hof, B, van Kooyk, Y, Geijtenbeek, TB	Immunity	2007