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Title: Regulation of ribosomal protein S6 phosphorylation by casein kinase 1 and protein phosphatase 1.

Authors: Hutchinson, John A; Shanware, Naval P; Chang, Haeyoon; Tibbetts, Randal S

Published In J Biol Chem, (2011 Mar 11)

Abstract: Ribosomal protein S6 (rpS6) is a critical component of the 40 S ribosomal subunit that mediates translation initiation at the 5'-m(7)GpppG cap of mRNA. In response to mitogenic stimuli, rpS6 undergoes ordered C-terminal phosphorylation by p70 S6 kinases and p90 ribosomal S6 kinases on four conserved Ser residues (Ser-235, Ser-236, Ser-240, and Ser-244) whose modification potentiates rpS6 cap binding activity. A fifth site, Ser-247, is also known to be phosphorylated, but its function and regulation are not well characterized. In this study, we employed phospho-specific antibodies to show that Ser-247 is a target of the casein kinase 1 (CK1) family of protein kinases. CK1-dependent phosphorylation of Ser-247 was induced by mitogenic stimuli and required prior phosphorylation of upstream S6 kinase/ribosomal S6 kinase residues. CK1-mediated phosphorylation of Ser-247 also enhanced the phosphorylation of upstream sites, which implies that bidirectional synergy between C-terminal phospho-residues is required to sustain rpS6 phosphorylation. Consistent with this idea, CK1-dependent phosphorylation of rpS6 promotes its association with the mRNA cap-binding complex in vitro. Additionally, we show that protein phosphatase 1 (PP1) antagonizes rpS6 C terminus phosphorylation and cap binding in intact cells. These findings further our understanding of rpS6 phospho-regulation and define a direct link between CK1 and translation initiation.

PubMed ID: 21233202 Exiting the NIEHS site

MeSH Terms: Casein Kinase I/genetics; Casein Kinase I/metabolism*; HEK293 Cells; Humans; Peptide Chain Initiation, Translational/physiology*; Phosphorylation/physiology; Protein Phosphatase 1/genetics; Protein Phosphatase 1/metabolism*; RNA Caps/genetics; RNA Caps/metabolism*; Ribosomal Protein S6 Kinases, 70-kDa/genetics; Ribosomal Protein S6 Kinases, 70-kDa/metabolism; Ribosomal Protein S6/genetics; Ribosomal Protein S6/metabolism*

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