RIOK2 phosphorylation by RSK promotes synthesis of the human small ribosomal subunit

Abstract

Ribosome biogenesis lies at the nexus of various signaling pathways coordinating protein synthesis with cell growth and proliferation. This process is regulated by well-described transcriptional mechanisms, but a growing body of evidence indicates that other levels of regulation exist. Here we show that the Ras/mitogen-activated protein kinase (MAPK) pathway stimulates post-transcriptional stages of human ribosome synthesis. We identify RIOK2, a pre-40S particle assembly factor, as a new target of the MAPK-activated kinase RSK. RIOK2 phosphorylation by RSK promotes cytoplasmic maturation of late pre-40S particles, which is required for optimal protein synthesis and cell proliferation. RIOK2 phosphorylation facilitates its release from pre-40S particles and its nuclear re-import, prior to completion of small ribosomal subunits. Our results bring a detailed mechanistic link between the Ras/MAPK pathway and the maturation of human pre-40S particles, which open a hitherto poorly explored area of ribosome biogenesis.

Phospho-proteomics reveals that RSK signaling is required for proliferation of natural killer cells stimulated with IL-2 or IL-15

“…Among the highly upregulated phospho-sites, this analysis highlighted plastin-2 (LCP1) S5 which regulates enzymatic activity and intracellular translocation (Koide et al, 2017) and the serine/threonine-protein kinase 17B (STK17B/DRAK2) S12 which negatively regulates IL-2 signaling and T cell development (Mandarano et al, 2020). Other phosphosites with known regulatory function included vimentin (VIM) pS56 (Li et al, 2016;Ratnayake et al, 2021), the serine/threonine-protein kinase PAK 2 (PAK2) pS141 (Li et al, 2011;Zhan et al, 2003), Wiskott-Aldrich syndrome protein (WAS) pS483 (Cory et al, 2003;Liu et al, 2013), 40S ribosomal protein S6 (RPS6) pS236 & pS240 (Cerezo et al, 2021;Salizzato et al, 2016) and stathmin (STMN1) pS25 (Alesi et al, 2016;Kuang et al, 2016Kuang et al, , 2015. Among the most downregulated phospho-sites with known regulatory function, we found stromal interaction molecule 1 (STIM1) pS608 (Casas-Rua et al, 2015;Pozo-Guisado et al, 2013;Tomas-Martin et al, 2015), mitochondrial fission factor (which was not certified by peer review) is the author/funder.…”

Phospho-proteomics reveals that RSK signaling is required for proliferation of natural killer cells stimulated with IL-2 or IL-15

“…Among the highly upregulated phospho-sites, this analysis highlighted plastin-2 (LCP1) S5 which regulates enzymatic activity and intracellular translocation (Koide et al, 2017) and the serine/threonine-protein kinase 17B (STK17B/DRAK2) S12 which negatively regulates IL-2 signaling and T cell development (Mandarano et al, 2020). Other phosphosites with known regulatory function included vimentin (VIM) pS56 (Li et al, 2016;Ratnayake et al, 2021), the serine/threonine-protein kinase PAK 2 (PAK2) pS141 (Li et al, 2011;Zhan et al, 2003), Wiskott-Aldrich syndrome protein (WAS) pS483 (Cory et al, 2003;Liu et al, 2013), 40S ribosomal protein S6 (RPS6) pS236 & pS240 (Cerezo et al, 2021;Salizzato et al, 2016) and stathmin (STMN1) pS25 (Alesi et al, 2016;Kuang et al, 2016Kuang et al, , 2015. Among the most downregulated phospho-sites with known regulatory function, we found stromal interaction molecule 1 (STIM1) pS608 (Casas-Rua et al, 2015;Pozo-Guisado et al, 2013;Tomas-Martin et al, 2015), mitochondrial fission factor (MFF) pS146 (Ducommun et al, 2015), and serine/threonine-protein phosphatase PP1γ catalytic subunit (PPP1CC) pT311 (Schmutz et al, 2011).…”