Disease relevance of Rps6

• We found that phosphorylation of two molecules downstream to it, ribosomal p70 S6 kinase (S6K) and ribosomal protein S6, was markedly suppressed by hypoxia [1].
• HIV antiretroviral agents inhibit protein synthesis and decrease ribosomal protein S6 and 4EBP1 phosphorylation in C2C12 myocytes [2].
• Hypertrophy of Pten-deficient neurons required the activity of the serine-threonine kinase mTor. mTor is a master regulator of cell and organ growth which can trigger a cascade of downstream signaling pathways involving, in part, components of the translational machinery, including S6k1 and its substrate the ribosomal protein S6 [3].
• The extent of phosphorylation of ribosomal protein S6 in the ascites cells themselves was low [4].
• The possible role of insulin-mediated phosphorylation of ribosomal protein S6 in the control of cell proliferation was examined in insulin-unresponsive mouse melanoma calls (PG19) and insulin-responsive melanoma x fibroblast clone 100A [5].

High impact information on Rps6

• Epidermal growth factor (10(-9)M), prostaglandin (8.5 X 10(-7)M), F2 alpha, and insulin (10(-9)M), each of which only leads to a partial phosphorylation of 40S ribosomal protein S6, generate the same first eight phosphopeptides induced by 10% serum, suggesting all three activate a common regulatory pathway for the phosphorylation of S6 [6].
• Addition of serum to resting cultures of Swiss mouse 3T3 cells causes an immediate multiple phosphorylation of 40S ribosomal protein S6 [7].
• Regulation of 40S ribosomal protein S6 phosphorylation in Swiss mouse 3T3 cells [7].
• Activation of the 70/85K S6 kinases (pp70S6k) by serine phosphorylation results in 40S ribosomal protein S6 phosphorylation and is important for G1 cell-cycle transition in a variety of cells [8].
• To study the effect of impaired ribosome functions in vivo, we conditionally deleted one or two alleles of the 40S ribosomal protein S6 gene in T cells in the mouse [9].

Biological context of Rps6

• Ribosomal protein S6 phosphorylation is a determinant of cell size and glucose homeostasis [10].
• Ribosomal protein S6 phosphorylation: from protein synthesis to cell size [11].
• Partial amino acid sequences were obtained from 22 internal tryptic peptides of rat liver p70s6k (M(r) 70,000 ribosomal protein S6 kinase), 3 of which were found to contain phosphorylated residues [12].
• To gain insight into the importance of this process during mouse oogenesis and embryonic development, we deleted one allele of the ribosomal protein S6 gene in growing oocytes and generated S6-heterozygous embryos [13].
• We previously reported that hydrogen peroxide (H2O2) mediates mitogen activation of ribosomal protein S6 kinase 1 (S6K1) which plays an important role in cell proliferation and growth [14].

Anatomical context of Rps6

• In this study the activation of the serine/threonine-specific ribosomal protein S6 kinases in response to IL-2 was analyzed in the murine T-cell line CTLL-20, a model system of IL-2-dependent proliferation [15].
• Treatment of 3T3-L1 cells with 0.1-1.0 nM insulin results in rapid (5-15 min) activation of a soluble protein kinase that phosphorylates serine residues in ribosomal protein S6 [16].
• The immunosuppressant rapamycin blocks p70s6k/p85s6k activation and phosphorylation of 40S ribosomal protein S6 in Swiss 3T3 cells [17].
• Treatment of quiescent 3T3 cells with sodium orthovanadate induces a 10-fold stimulation of a kinase that phosphorylates ribosomal protein S6 [18].
• Insulin-sensitive, serum-sensitive protein kinase activity that phosphorylates ribosomal protein S6 in cultured fibroblast-melanoma hybrid cells [19].

Associations of Rps6 with chemical compounds

• Purification and characterization of a 40 S ribosomal protein S6 kinase from vanadate-stimulated Swiss 3T3 cells [20].
• Considerable biochemical and pharmacological evidence suggests that the activation of ribosomal protein S6 kinases (S6Ks) by activated receptor tyrosine kinases involves multiple co-ordinated input signals [21].
• In mice fed chow containing the synthetic protease inhibitor camostat, protein synthetic rates and phosphorylation of two downstream targets of mTOR, eukaryotic initiation factor 4E binding protein 1 (4E-BP1) and the ribosomal protein S6 (S6), increased in comparison with fasted controls [22].
• This protein is apparently a serine/threonine kinase and is most closely related to the amino-terminal half of the ribosomal protein S6 kinase II first characterized in Xenopus eggs (42% overall identity and 56% identity in the predicted catalytic domain) [23].
• Previously, we have shown that in Abelson-transformed cells, the Abelson kinase regulates the phosphoserine content of ribosomal protein S6 [24].

Enzymatic interactions of Rps6

• Extracts from epidermal growth factor (EGF)-stimulated Swiss mouse 3T3 cells are up to 10 times more potent in phosphorylating ribosomal protein S6 than extracts from quiescent cells [25].

Regulatory relationships of Rps6

• Rapamycin abolished the effects of insulin on increasing phosphorylation of ribosomal protein S6 and on activating p70S6K [26].
• Protease-activated kinase II as the mediator of epidermal growth factor-stimulated phosphorylation of ribosomal protein S6 [27].

Other interactions of Rps6

• The bt-Erk-1 protein also had the capacity to reactivate the ribosomal protein S6 kinase (S6KII) [28].
• Notably, Pml-/- cells and tumours display higher sensitivity both in vitro and in vivo to growth inhibition by rapamycin, and lack of PML inversely correlates with phosphorylation of ribosomal protein S6 and tumour angiogenesis in mouse and human tumours [29].
• They also phosphorylated MBP and microtubule-associated protein 2 but not 40S ribosomal protein S6 [30].
• Particulate preparations from insulin-treated 3T3-L1 cells retain the enhanced ability to incorporate 32P from [gamma-32P]ATP into ribosomal protein S6 (Smith, C. J., Rubin, C. S., and Rosen, O. M. (1980) Proc. Natl. Acad. Sci. U. S. A. 77, 2641-2645) [31].
• Differential stimulation of phosphorylation of initiation factors eIF-4F, eIF-4B, eIF-3, and ribosomal protein S6 by insulin and phorbol esters [32].

Analytical, diagnostic and therapeutic context of Rps6

• Characterization of the Rps6 provides a basis to study the functions of the mammalian S6 by gene targeting [33].
• The extent of phosphorylation of ribosomal protein S6 in the livers of mice carrying the Krebs II ascites tumour has been examined by two-dimensional gel electrophoresis [4].

References