Phosphorylation of ribosomes

Nielsen, P. J., Manchester, K. L., Towbin, H., Gordon, J., and Thomas, G. (1982) The phosphorylation of ribosomal protein S6 in rat tissues following cycloheximide injection, in diabetes, and after denervation of diaphragm. J. Biol. Chem. 257, 12316-12321. 

There is recent data to suggest that there may in fact be a biological role for the internalized insulin and EGF receptors (both of which are themselves tyrosine kinases). Thus, microinjection of insulin-occupied insulin receptors into Xenopus oocytes causes the increased phosphorylation of ribosomal protein S6 (a known substrate for the insulin receptor/kinase) [62] and the EGF receptor in endocytic vesicles has been shown to retain its kinase activity [63]. Whether the internalized insulin receptor/kinase or EGF receptor/kinase has a physiological role or not is as yet unknown. Clearly, though, these data suggest that there is much more to be learned about the role of internalized hormone-receptor complexes, especially those where the receptor possesses intrinsic enzymatic activity. 

Activated PKB (Akt) phosphorylates the following proteins with the indicated anabolic consequences Bad phosphorylation yields P-Bad which then dissociates from a Bcl-2-Bcl-X] complex in the mitochondrial outer membrane and is sequestered by 14.3.3 proteins. Mitochondrial pore blockage by the Bad-free Bcl-2-Bcl-xL complex successively prevents cytochrome c release from mitochondria, blocks procaspase activation by cytochrome c and thus inhibits apoptosis and increases cell survival. Phosphorylation of p70S6 kinase by PKB results in activation of this PK, phosphorylation of ribosomal small subunit protein S6 and enhancement of translation (protein synthesis). Phosphorylation of glycogen synthase (GS) kinase 3 (GSK3) by PKB results in an inactive P-GSK3, a consequent increase in the amount of the active non-phosphorylated form of GS and increased glycogen synthesis. 

Hanocq-Quertier J, Baltus E. 1981. Phosphorylation of ribosomal proteins during maturation of Xenopus laevis oocytes. Eur J Biochem 120(2) 351-355. 

Nielsen PJ, Thomas G, Mailer JL. 1982. Increased phosphorylation of ribosomal protein S6 during meiotic maturation of Xenopus oocytes. Proc Natl Acad Sci USA 79(9) 2937-2941. 

Spivack JC, Erikson RL, Mailer JL. 1984. Microinjection of pp60v-src into Xenopus oocytes increases phosphorylation of ribosomal protein S6 and accelerates the rate of progesterone-induced meiotic maturation. Mol Cell Biol 4(8) 1631-1634. 

Traugh, J.A., Mumby, M., Traut, R.R. Phosphorylation of ribosomal protein by substrate-specific protein kinases from rabbit reticulocytes. Proc. nat. Acad. Sci. (Wash.) 70, 373-376 (1973)... 

Majumder, G.C., Turkington, R.W. Hormone-dependent phosphorylation of ribosomal and plasma membrane proteins in mouse mammary gland in vitro. J. biol. Chem. 247, 7207-7217 (1972)... 

Fig. 2. Effect of phytohormones on phosphorylation of ribosomal protein S< in detached pumpkin cotyledons. The autoradiograms of one-dimensional SDS gel electrophoresis of ribosomal proteins isolated from pumpkin cotyledons. Cotyledons were incubated for 6 h in water a and in solution of b ABA (10 M) c BA (5x lO M) or d BA-I-ABA in the same concentrations respectively. Discs from cotyledons were then labeled for 2 h with P (50 jnCi/ml). and isolated ribosomal proteins were subjected to electrophoresis [26]...

To what extent reversible modiflcations of ribosomal constituents are involved in translational control of protein synthesis is uncertain. Although phosphorylation of ribosomal protein S6 increases with cell proliferation, it is not known whether this change is directly related to the accompanying increase in protein synthesis by an effect on the translation rate. 

Kruppa J, Clemens MJ. Differential kinetics of changes in the state of phosphorylation of ribosomal protein S6 and in the rate of protein synthesis in MPC 11 cells during tonicity shifts. EMBO J 1984 3 95-100. 

Luiken JJ, Blommaart EF, Boon L, van Woerkom GM, Meijer AJ. Cell swelling and the control of autophagic proteolysis in hepatocytes involvement of phosphorylation of ribosomal protein S6 Biochem Soc Trans 1994 22 508-511. 

Rosen, O. M., Rubin, C. S., Cobb, M. H., and Smith, C. J., 1981, Insulin stimulates the phosphorylation of ribosomal protein S6 in a cell-free system derived from 3T3-L1 adipocytes, J. Biol. Chem. 256 3630. 

Virus-specific phosphorylation of ribosomal proteins and/or proteins associated with ribosome preparations has been described (Ter-shak, 1978 James and Tershak, 1981) and thought to be a possible regulatory reaction involved in inhibition of cellular protein synthesis. Although no data are available to relate the phosphorylation events with the regulation of protein synthesis, it is interesting that one of... 

Kaerlein, M., and Horak, I., 1976, Phosphorylation of ribosomal proteins in HeLa cells infected with vaccinia virus. Nature (London) 259 250. 

S6K1 (also known as p70S6 kinase) is a serine/ threonine protein kinase which is involved in the regulation of translation by phosphorylating the 40S ribosomal protein S6. Insulin and several growth factors activate the kinase by phosphorylation in a PI 3-kinase dependent and rapamycin-sensitive manner. Phosphorylation of S6 protein leads to the translation of mRNA with a characteristic 5 polypyrimidine sequence motif. 

Mazroui, R., Sukarieh, R., Bordeleau, M. E., Kaufman, R. J., Northcote, P., Tanaka, J., Gallouzi, I., and Pelletier, J. (2006). Inhibition of ribosome recruitment induces stress granule formation independendy of eukaryotic initiation factor 2alpha phosphorylation. Mol. Biol. Cell 17, 4212-4219. 

The main method through which these agents regulate the translational apparatus is via changes in the states of phosphorylation of translation factors and related proteins phosphorylation may, for example, alter the intrinsic activity of translation factors or affect their ability to bind other components (other factors, the ribosome, or RNA). 

Figure 13.1 Schematic diagram of eukaryotic translation initiation. The sites of action of small molecule inhibitors are shown with dashed lines. Kinases that affect the phosphorylation of 4E-BP and eIF2a, and exert effects on ribosome recruitment and ternary complex formation, respectively, are shown in a black box. See text for details.

A strong link between the phosphorylation of nucleolin, its proteolysis and the production of ribosomal RNA has been observed (Bouche et al, 1984 Bourbon et al, 1983 Warrener and Petryshyn, 1991). The inhibition of proteolysis using leupeptin leads to a lower rRNA transcription in an in vitro transcription system (Bouche et al, 1984). In another series of experiments, the injection of nucleolin antiserum leads to 2-3.5 fold stimulation of pre-rRNA synthesis in Chironomus tentans salivary glands (Egyhazi et al, 1988), although it was not clearly demonstrated that these antibodies blocked specifically the homolog of nucleolin in this species. A model was proposed based on these observations where nucleolin was... 

Suzuki N, Kobayashi M, Sahara K, Suzuki T, Hosoya T (1991) Synergistic stimulatory effect of glucocorticoid, EGF and insulin on the synthesis of ribosomal RNA and phosphorylation of nucleolin in primary cultured rat hepatocytes. Biochim Biophys Acta 1092 367-375 Suzuki N, Matsui H, Hosoya T (1985) Effects of androgen and polyanrines on the phosphorylation of nucleolar proteins from rat ventral prostates with particular reference to 110-kDa phosphoprotein. J Biol Chem 260 8050-8055... 

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