Ribosomal S6 kinases

Poteet-Smith, C. E., Smith, J. A., Lannigan, D. A., Freed, T. A., and Sturgill, T. W. (1999). Generation of constitutively active p90 ribosomal S6 kinase in vivo. Implications for the mitogen-activated protein kinase-activated protein kinase family. J. Biol. Chem. 274, 22135-22138. 

CDK, cyclin-dependent kinase ERK, extracellular signal-regulated kinase GRK, G protein receptor kinase JNK, Jun kinase MAP kinase, mitogen activated protein kinase MEK, MAP kinase and ERK kinases RSK, ribosomal S6 kinase, GSK, glycogen synthase kinase SAPK, stress-activated protein kinase SEK, SAPK kinase. 

There are at least three major effector pathways that are activated by neurotrophic factor-Trk receptors. The best-characterized pathway is the extracellular-regulated kinase (ERK) cascade, which is regifiated by activation of Ras, a small membrane-bound G protein. Activation of Ras occurs when activated Trk receptor associates with adaptor proteins and a GTP exchange factor (see Russell and Duman 2002 for details). Ras in turn recruits and activates a serine threonine kinase, Raf, to the membrane resulting in the activation of ERK kinase (also referred to as MEK) and ERK (also known as mitogen activated protein kinase or MAPK). Activation of the Ras-Raf-MEK-ERK cascade can lead to regifiation of many celMar proteins, including ribosomal S6-kinase (RSK). 

VCAM) in a NF-KB-dependent manner (Tummala et al. 1999). The link between ATiR and NF-kB activation involves direct phosphorylation of the p65 subunit of NF-kB by ribosomal S6 kinase (RSK) and by IKK, and both pathways appear to be redox-dependent (Zhang et al. 2005a,b). 

Frodin, M., and S. Gammeltoft. 1999. Role and regulation of 90kDa ribosomal S6 kinase (RSK) in signal transduction. Mol. Cell. Endocrinol. 151 65-77. 

Dufner A, Thomas G. Ribosomal S6 kinase signaling and the control of translation. Exp. Cell. Res. 1999 253 100-109. 

PAPKOFF J, Chen R-H, BLENIS J, FORSMAN J. p42 mitogen-activated protein kinase and p90 ribosomal S6 kinase are sriecdvely phosphorylated and activated during thrombin-induced platelet activation and aggregation. Mol Cdl Biol 14 463-472,1994. 

MAPKAP-K MAPK-activated protein kinase MNK mitogen-activated protein kinase-interacting kinase MSK mitogen- and stress-activated protein kinase PRAK p38-regulated/activated protein kinase RSK 90kDa-ribosomal S6 kinase. 

An important cytoplasmic substrate of ERK1/2 proteins is the 90 kDa ribosomal S6 kinase (RSK), also termed MAPK-activated protein kinase 1, MAPKAP-K1. This enzyme is activated by phosphorylation in the activation loop. A number of cellular functions of RSK have been proposed, including phosphorylation of transcription factors like CREB and NFkB as well as stimulation of protein biosynthesis by phosphorylation of the ribsomal protein S6. 

Catalytic amplification occurs when one enzyme modifies a large number, say TV, of the molecules being controlled. Hence, one molecule of regulator enzyme affects TV molecules of the enzyme being controlled, an amplification factor of TV. For example, MAP kinase activates the protein ribosomal S6 kinase (Rsk) each molecule of MAP kinase can phosphorylate many molecules of Rsk, giving catalytic amplification (Fig. 31.13). 

Several proteins are substrates for MAPK, both in vivo and in vitro (for reviews, see Pelech and Sanghera, 1992 Davis, 1993). Physiological candidate substrates include proteins involved in cell proliferation and growth c-fos, c-myc, c-jun, the 90-kDa ribosomal S6 kinase or p90 , oncoprotein 18, the phosphorylated heat- and acid-stable protein regulated by insulin or PHAS-I), cell signaling (cytoplasmic phospholipase... 

Ribosomal S6 kinase 27 Modeller ligand Accelrys 837 NCI, volume and 2 10.5 — 1C5o = 1iiM [23]... 

Pelech SL, Meijer L, Krebs EG. 1987. Characterization of maturation-activated histone HI and ribosomal S6 kinases in sea star oocytes. Biochemistry 26(24) 7960-7968. 

Sugiura K, Naito K, Iwamori N, Kagii H, Goto S, Ohashi S, Naruoka H, Yada E, Yamanouchi K, Tojo H. 2002. Activation of ribosomal S6 kinase (RSK) during porcine oocyte maturation. Zygote 10(l) 31-36. 

In contrast, several lines of evidence suggest that the activation of the Ras-Raf-ERKl/2 pathway may oppose JNK-mediated effects with respect to mitochondria-dependent apoptosis (Fig. 4). ERKl/2 can phosphorylate and activate mitogen-and stress-activated kinase 1 (MSKl) and pp90 ribosomal S6 kinase (RSK) [83,84]. RSK can phosphorylate BAD, thereby inhibiting its proapoptotic effects [83]. Furthermore, both RSK and MSKl are potent activators of cyclic adenosine monophosphate (cAMP) element binding protein (CREB), a transcription factor for Blc-2, and therefore important for cell survival [84]. The upregulation or overexpression of Bcl-2 has been reported to be associated with the inactivation of JNK [75,85]. Thus, ERKl/2 activation could ultimately lead to JNK inactivation. Finally, the activation of c-Ras has been shown to result in a suppression of Bax expression, via a mechanism that involved activation of both the ERKl/2 signaling cascade and the phosphatidylinositol-3 -kinase (PI-3)/Akt pathway [80]. 

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