High impact information on RPS6KA4

• The Kinases MSK1 and MSK2 Are Required for Epidermal Growth Factor-induced, but Not Tumor Necrosis Factor-induced, Histone H3 Ser10 Phosphorylation [1].
• The sequences between the two catalytic domains and of the C-terminal extension contain elements that control RSKB activity [2].
• Alanine mutation of the key Phe709 residue resulted in strongly elevated basal level RSKB activity [2].
• RSKB activation depended on phosphorylation of linker Ser(343) and Ser(360) and associated with phosphorylation of nonconserved Ser(347), but Ser(347)-deficient RSKB retained partial activity [3].
• Treatment of HeLa cells with tumor necrosis factor, epidermal growth factor, phorbol 12-myristate 13-acetate, and ionomycin but not with insulin resulted in strong activation of endogenous RSKB [3].

Biological context of RPS6KA4

• RSK-B presents two catalytic domains typical for the RSK family [4].
• Unlike other RSKs, the activation loop phosphorylation sites of both catalytic domains of RSKB, Ser(196) and Thr(568), were required for activity [3].
• The MSK2 and HSK2 genes exhibit a common structure of 13 exons, including a 15-nucleotide alternatively spliced exon 8 [5].
• The HSK2 promoter contains a GC-rich region, not present in the mouse promoter, and has few transcription factor binding sites in common with MSK2 [5].
• Exon 1 and its 5'-flanking sequence are highly divergent between the two species, and intron 1 of the HSK2 gene contains a region similar to the MSK2 promoter sequence, suggesting that it may be the remnant of a now-superceded regulatory region [5].

Anatomical context of RPS6KA4

• RSK-B locates to the cell nucleus and co-translocates p38alphaMAPK [4].

Enzymatic interactions of RPS6KA4

• RSK-B phosphorylates the cAMP response element-binding protein (CREB) and c-Fos peptides [4].

Other interactions of RPS6KA4

• In conclusion, RSK-B is a novel CREB kinase under dominant p38alphaMAPK control, also phosphorylating additional substrates [4].
• RSK-B is a p38alphaMAPK substrate, and activated by p38alphaMAPK and, more weakly, by ERK1 [4].
• MSK2 activity was low, relative to MSK1, with little activation post-exercise [6].
• In intracellular assays, RSK-B drives cAMP response element- and AP1-dependent reporter expression [4].

References