Genomes and Genes
70 kda ribosomal protein s6 kinases
Summary: A family of ribosomal protein S6 kinases that are considered the major physiological kinases for RIBOSOMAL PROTEIN S6. Unlike RIBOSOMAL PROTEIN S6 KINASES, 90KDa the proteins in this family are sensitive to the inhibitory effects of RAPAMYCIN and contain a single kinase domain. They are referred to as 70kDa proteins, however ALTERNATIVE SPLICING of mRNAs for proteins in this class also results in 85kDa variants being formed.
- Zhou H, Wong A. Activation of p70S6K induces expression of matrix metalloproteinase 9 associated with hepatocyte growth factor-mediated invasion in human ovarian cancer cells. Endocrinology. 2006;147:2557-66 pubmed..These data suggest that interfering p70(S6K) may provide a novel means of controlling tumor cell invasiveness. ..
- Liu L, Li F, Cardelli J, Martin K, Blenis J, Huang S. Rapamycin inhibits cell motility by suppression of mTOR-mediated S6K1 and 4E-BP1 pathways. Oncogene. 2006;25:7029-40 pubmed..Rapamycin inhibits IGF-I-stimulated cell motility, through suppression of both S6K1 and 4E-BP1/eIF4E-signaling pathways, as a consequence of inhibition of mTOR kinase activity. ..
- Pardo O, Wellbrock C, Khanzada U, Aubert M, Arozarena I, Davidson S, et al. FGF-2 protects small cell lung cancer cells from apoptosis through a complex involving PKCepsilon, B-Raf and S6K2. EMBO J. 2006;25:3078-88 pubmed..However, increased S6K1 kinase activity has no such effect. Thus, S6K2 but not S6K1 mediates prosurvival/chemoresistance signalling. ..
- Qiao J, Kang J, Ishola T, Rychahou P, Evers B, Chung D. Gastrin-releasing peptide receptor silencing suppresses the tumorigenesis and metastatic potential of neuroblastoma. Proc Natl Acad Sci U S A. 2008;105:12891-6 pubmed publisher..Our findings demonstrate that GRP and GRP-R have important oncogenic properties beyond their established mitogenic functions. Therefore, GRP-R may be an ideal therapeutic target for the treatment of aggressive neuroblastomas. ..
- Lin S, Chang C, Ng A, Wang S, Li J, Hu C. Prevention of TGF-beta-induced apoptosis by interlukin-4 through Akt activation and p70S6K survival signaling pathways. Apoptosis. 2007;12:1659-70 pubmed
- Martin N, Schwamborn K, Urlaub H, Gan B, Guan J, Dejean A. Spatial interplay between PIASy and FIP200 in the regulation of signal transduction and transcriptional activity. Mol Cell Biol. 2008;28:2771-81 pubmed publisher..Altogether, these results provide the first evidence for the existence of a close-spatially controlled-mode of regulation of FIP200 and PIASy nucleocytoplasmic functions. ..
- Kenerson H, Folpe A, Takayama T, Yeung R. Activation of the mTOR pathway in sporadic angiomyolipomas and other perivascular epithelioid cell neoplasms. Hum Pathol. 2007;38:1361-71 pubmed..This suggests the possibility that mTOR inhibitors such as rapamycin may be therapeutic for this class of disease...
- Abe Y, Yoon S, Kubota K, Mendoza M, Gygi S, Blenis J. p90 ribosomal S6 kinase and p70 ribosomal S6 kinase link phosphorylation of the eukaryotic chaperonin containing TCP-1 to growth factor, insulin, and nutrient signaling. J Biol Chem. 2009;284:14939-48 pubmed publisher..Although the molecular mechanism of CCTbeta regulation remains unclear, our findings demonstrate a link between oncogene and growth factor signaling and chaperonin CCT-mediated cellular activities. ..
- Jiang X, Sinnett Smith J, Rozengurt E. Carbachol induces p70S6K1 activation through an ERK-dependent but Akt-independent pathway in human colonic epithelial cells. Biochem Biophys Res Commun. 2009;387:521-4 pubmed publisher..These findings imply that GPCR activation induces p70S6K1 via ERK rather than through the canonical PI 3-kinase/Akt/TSC/mTORC1 pathway in T84 colon carcinoma cells. ..
- Terzis G, Spengos K, Mascher H, Georgiadis G, Manta P, Blomstrand E. The degree of p70 S6k and S6 phosphorylation in human skeletal muscle in response to resistance exercise depends on the training volume. Eur J Appl Physiol. 2010;110:835-43 pubmed publisher..These findings indicate that when exercise is performed in a fasted state, the increase in phosphorylation of signalling molecules such as p70(S6k) and the S6 ribosomal protein in human muscle depends on the exercise volume. ..
- Palaniappan M, Menon K. Human chorionic gonadotropin stimulates theca-interstitial cell proliferation and cell cycle regulatory proteins by a cAMP-dependent activation of AKT/mTORC1 signaling pathway. Mol Endocrinol. 2010;24:1782-93 pubmed publisher..Taken together, the present studies show a novel intracellular signaling pathway for T-I cell proliferation involving LH/hCG-mediated activation of the AKT/mTORC1 signaling cascade. ..
- Deldicque L, Atherton P, Patel R, Theisen D, Nielens H, Rennie M, et al. Decrease in Akt/PKB signalling in human skeletal muscle by resistance exercise. Eur J Appl Physiol. 2008;104:57-65 pubmed publisher..The present results indicate that high-intensity resistance exercise in the fasted state inhibits Akt/PKB and 4E-BP1 whilst concomitantly augmenting MAPK signalling and p70(s6k) on Thr421/Ser424. ..
- Taliaferro Smith L, Nagalingam A, Zhong D, Zhou W, Saxena N, Sharma D. LKB1 is required for adiponectin-mediated modulation of AMPK-S6K axis and inhibition of migration and invasion of breast cancer cells. Oncogene. 2009;28:2621-33 pubmed publisher..Our findings indicate the possibility of using adiponectin analogues to inhibit invasion and migration of breast cancer cells. ..
- Zatelli M, Minoia M, Martini C, Tagliati F, Ambrosio M, Schiavon M, et al. Everolimus as a new potential antiproliferative agent in aggressive human bronchial carcinoids. Endocr Relat Cancer. 2010;17:719-29 pubmed publisher..Our data demonstrate that everolimus reduces VEGF secretion and cell viability in BCs with a mechanism likely involving IGF1 signaling, suggesting that it might represent a possible medical treatment for BCs. ..
- Kleinz M, Baxter G. Apelin reduces myocardial reperfusion injury independently of PI3K/Akt and P70S6 kinase. Regul Pept. 2008;146:271-7 pubmed..8+/-8.8%, n=4). In conclusion these results suggest that apelin may be a new and potentially important cardioprotective autacoid, upregulated rapidly after myocardial ischaemia and acting through an unknown pathway. ..
- Hu X, Zhang Q, Yang J, Liu C, Zhang Z, Wang J, et al. [The expression of mammalian target of rapamycin and its substrates in autogenous vein graft in rats]. Zhonghua Wai Ke Za Zhi. 2006;44:1053-7 pubmed
- Nishioka C, Ikezoe T, Yang J, Takeshita A, Taniguchi A, Komatsu N, et al. Blockade of MEK/ERK signaling enhances sunitinib-induced growth inhibition and apoptosis of leukemia cells possessing activating mutations of the FLT3 gene. Leuk Res. 2008;32:865-72 pubmed..Taken together, concomitant blockade of FLT3 and MEK signaling represents a promising treatment strategy for individuals with leukemia who possess activating mutations of FLT3. ..
- Distefano G, Boca M, Rowe I, Wodarczyk C, Ma L, Piontek K, et al. Polycystin-1 regulates extracellular signal-regulated kinase-dependent phosphorylation of tuberin to control cell size through mTOR and its downstream effectors S6K and 4EBP1. Mol Cell Biol. 2009;29:2359-71 pubmed publisher..We provide a detailed molecular mechanism by which PC-1 can inhibit the mTOR pathway and regulate cell size. ..
- Sacco A, Morcavallo A, Pandini G, Vigneri R, Belfiore A. Differential signaling activation by insulin and insulin-like growth factors I and II upon binding to insulin receptor isoform A. Endocrinology. 2009;150:3594-602 pubmed publisher..These results underline the role of IR-A in physiology and disease. ..
- Schaafsma D, McNeill K, Stelmack G, Gosens R, Baarsma H, Dekkers B, et al. Insulin increases the expression of contractile phenotypic markers in airway smooth muscle. Am J Physiol Cell Physiol. 2007;293:C429-39 pubmed..This could have important implications for the use of recently approved aerosolized insulin formulations in diabetes mellitus. ..
- Yang Y, Ikezoe T, Nishioka C, Taguchi T, Zhu W, Koeffler H, et al. ZD6474 induces growth arrest and apoptosis of GIST-T1 cells, which is enhanced by concomitant use of sunitinib. Cancer Sci. 2006;97:1404-9 pubmed..The combination of ZD6474 and sunitinib should be investigated further. ..
- Sanchez Canedo C, Demeulder B, Ginion A, Bayascas J, Balligand J, Alessi D, et al. Activation of the cardiac mTOR/p70(S6K) pathway by leucine requires PDK1 and correlates with PRAS40 phosphorylation. Am J Physiol Endocrinol Metab. 2010;298:E761-9 pubmed publisher..We conclude that the leucine-induced stimulation of the cardiac PRAS40/mTOR/p70(S6K) pathway requires PDK1 in a way that differs from that of insulin. ..
- Trinh X, Tjalma W, Vermeulen P, Van den Eynden G, Van der Auwera I, Van Laere S, et al. The VEGF pathway and the AKT/mTOR/p70S6K1 signalling pathway in human epithelial ovarian cancer. Br J Cancer. 2009;100:971-8 pubmed publisher..Although VEGF-A inhibitors are classified as anti-angiogenic drugs, these data suggest that the working mechanism has an important additional modality of targeting the tumour cells directly. ..
- Okada T, Sawada T, Kubota K. Rapamycin inhibits growth of cholangiocarcinoma cells. Hepatogastroenterology. 2009;56:6-10 pubmed..Rapamycin offers a new therapeutic strategy to inhibit the growth of cholangiocarcinoma. ..
- Liu L, Zheng J, Wang X, Jiang B. Endothelial p70 S6 kinase 1 in regulating tumor angiogenesis. Cancer Res. 2008;68:8183-8 pubmed publisher..This study helps to understand the role and molecular mechanism of p70S6K1 in regulating angiogenesis and tumor growth, and the role of endothelial p70S6K1/HIF-1 signaling in the regulation of tumor microenvironment and angiogenesis. ..
- Ono H, Pocai A, Wang Y, Sakoda H, Asano T, Backer J, et al. Activation of hypothalamic S6 kinase mediates diet-induced hepatic insulin resistance in rats. J Clin Invest. 2008;118:2959-68 pubmed publisher..These results suggest that activation of hypothalamic S6K contributes to hepatic insulin resistance in response to short-term nutrient excess. ..
- Morita T, Sobue K. Specification of neuronal polarity regulated by local translation of CRMP2 and Tau via the mTOR-p70S6K pathway. J Biol Chem. 2009;284:27734-45 pubmed publisher..Taken together, we conclude that the local translation of CRMP2 and Tau, regulated by mTOR-p70S6K, is critical for the specification of neuronal polarity. ..
- Varma S, Khandelwal R. Effects of rapamycin on cell proliferation and phosphorylation of mTOR and p70(S6K) in HepG2 and HepG2 cells overexpressing constitutively active Akt/PKB. Biochim Biophys Acta. 2007;1770:71-8 pubmed..525, p<0.0001). These results suggest that rapamycin causes a decline in the cell growth through the inhibition of mTOR. ..
- Cen L, Arnoczky K, Hsieh F, Lin H, Qualman S, Yu S, et al. Phosphorylation profiles of protein kinases in alveolar and embryonal rhabdomyosarcoma. Mod Pathol. 2007;20:936-46 pubmed..These protein kinases may play roles in the development or tumor progression of rhabdomyosarcomas and thus may serve as novel targets for therapeutic intervention...
- Zhou Q, Jiang Z, Holik J, Chawla A, Hagan G, Leszyk J, et al. Akt substrate TBC1D1 regulates GLUT1 expression through the mTOR pathway in 3T3-L1 adipocytes. Biochem J. 2008;411:647-55 pubmed publisher..Taken together, our data suggest that TBC1D1 may be involved in controlling GLUT1 glucose transporter expression through the mTOR-p70 S6 kinase pathway. ..
- Lafay Chebassier C, Perault Pochat M, Page G, Rioux Bilan A, Damjanac M, Pain S, et al. The immunosuppressant rapamycin exacerbates neurotoxicity of Abeta peptide. J Neurosci Res. 2006;84:1323-34 pubmed..These results demonstrate that mTOR plays an important role as a cellular survival pathway in Abeta toxicity and could represent a possible target for modulating Abeta toxicity. ..
- Carloni S, Girelli S, Scopa C, Buonocore G, Longini M, Balduini W. Activation of autophagy and Akt/CREB signaling play an equivalent role in the neuroprotective effect of rapamycin in neonatal hypoxia-ischemia. Autophagy. 2010;6:366-77 pubmed..When the autophagic or the PI3K-Akt-mTOR pathways are interrupted cells undergo necrotic cell death. ..
- Lai K, Leong W, Chau J, Jia D, Zeng L, Liu H, et al. S6K1 is a multifaceted regulator of Mdm2 that connects nutrient status and DNA damage response. EMBO J. 2010;29:2994-3006 pubmed publisher..S6K1-Mdm2 interaction presents a route for cells to incorporate the metabolic/energy cues into DNA damage response and links the aging-controlling Mdm2-p53 and mTOR-S6K pathways. ..
- Terzis G, Georgiadis G, Stratakos G, Vogiatzis I, Kavouras S, Manta P, et al. Resistance exercise-induced increase in muscle mass correlates with p70S6 kinase phosphorylation in human subjects. Eur J Appl Physiol. 2008;102:145-52 pubmed
- Tesseraud S, Metayer S, Duchêne S, Bigot K, Grizard J, Dupont J. Regulation of protein metabolism by insulin: value of different approaches and animal models. Domest Anim Endocrinol. 2007;33:123-42 pubmed..Finally, although the role of insulin has been doubtful and has long been considered to be minor in ruminants and in avian species, this hormone clearly regulates protein metabolism in both species. ..
- Rose M. Interferon-gamma and intimal hyperplasia. Circ Res. 2007;101:542-4 pubmed
- Clements D, Asprey S, McCulloch T, Morris T, Watson S, Johnson S. Analysis of the oestrogen response in an angiomyolipoma derived xenograft model. Endocr Relat Cancer. 2009;16:59-72 pubmed publisher..This model may prove useful for studying the biology and effect of drugs on angiomyolipoma and diseases related to TSC. ..
- Gordon I, Ye F, Kent M. Evaluation of the mammalian target of rapamycin pathway and the effect of rapamycin on target expression and cellular proliferation in osteosarcoma cells from dogs. Am J Vet Res. 2008;69:1079-84 pubmed publisher..These data support the molecular basis for further investigation into the use of mTOR inhibitors as an antineoplastic approach for dogs with osteosarcoma. ..
- Matsuo M, Yamada S, Koizumi K, Sakurai H, Saiki I. Tumour-derived fibroblast growth factor-2 exerts lymphangiogenic effects through Akt/mTOR/p70S6kinase pathway in rat lymphatic endothelial cells. Eur J Cancer. 2007;43:1748-54 pubmed
- Kent M, Collins C, Ye F. Activation of the AKT and mammalian target of rapamycin pathways and the inhibitory effects of rapamycin on those pathways in canine malignant melanoma cell lines. Am J Vet Res. 2009;70:263-9 pubmed publisher..Use of mTOR inhibitors as antineoplastic treatments in dogs with melanoma warrants investigation. Furthermore, these data support the use of canine melanoma cells as a molecular model for melanoma in humans. ..
- Wu W, Lee C, Hsin C, Du J, Hsu T, Lin T, et al. TGF-beta inhibits prolactin-induced expression of beta-casein by a Smad3-dependent mechanism. J Cell Biochem. 2008;104:1647-59 pubmed publisher..Taken together, our results demonstrate that TGF-beta abrogates prolactin-stimulated beta-casein gene expression in mammary epithelial cells through, at least in part, a Smad3-dependent mechanism...
- Baba H, Wohlschlaeger J, Cicinnati V, Hilgard P, Lang H, Sotiropoulos G, et al. Phosphorylation of p70S6 kinase predicts overall survival in patients with clear margin-resected hepatocellular carcinoma. Liver Int. 2009;29:399-405 pubmed publisher..Activation of p70S6 kinase indicates aggressive tumour behaviour in patients with clear margin-resected HCC. Identification of p-p70S6 kinase in HCC selects high-risk patients who may benefit from drugs targeting the mTOR pathway. ..
- Musiolik J, van Caster P, Skyschally A, Boengler K, Gres P, Schulz R, et al. Reduction of infarct size by gentle reperfusion without activation of reperfusion injury salvage kinases in pigs. Cardiovasc Res. 2010;85:110-7 pubmed publisher..05). Gentle reperfusion reduces infarct size in pigs, but RISK activation is not causally involved in this infarct size reduction. ..
- Vazquez Martin A, Oliveras Ferraros C, Colomer R, Brunet J, Menendez J. Low-scale phosphoproteome analyses identify the mTOR effector p70 S6 kinase 1 as a specific biomarker of the dual-HER1/HER2 tyrosine kinase inhibitor lapatinib (Tykerb) in human breast carcinoma cells. Ann Oncol. 2008;19:1097-109 pubmed publisher
- Byrne R, Rosivatz E, Parsons M, Larijani B, Parker P, Ng T, et al. Differential activation of the PI 3-kinase effectors AKT/PKB and p70 S6 kinase by compound 48/80 is mediated by PKCalpha. Cell Signal. 2007;19:321-9 pubmed..The latter is only activated by higher doses of c48/80 resulting in an inhibition of the c48/80 induced PKB phosphorylation, thus explaining the observed biphasic activation profile for PKB in response to this secretagogue. ..
- Lee W, Kim Y, Choi J, Brooks S, Lee M, Kim S. Oltipraz and dithiolethione congeners inhibit hypoxia-inducible factor-1alpha activity through p70 ribosomal S6 kinase-1 inhibition and H2O2-scavenging effect. Mol Cancer Ther. 2009;8:2791-802 pubmed publisher..Oltipraz inhibits HIF-1alpha activity and HIF-1alpha-dependent tumor growth, which may result from a decrease in HIF-1alpha stability through S6K1 inhibition in combination with an H(2)O(2)-scavenging effect. ..
- Rice K, Desai D, Preston D, Wehner P, Blough E. Uniaxial stretch-induced regulation of mitogen-activated protein kinase, Akt and p70 S6 kinase in the ageing Fischer 344 x Brown Norway rat aorta. Exp Physiol. 2007;92:963-70 pubmed..Taken together, these data may help to explain, in part, the age-related changes in vascular morphology, function and response to injury. ..
- Ma B, Lui V, Hui E, Lau C, Ho K, Ng M, et al. The activity of mTOR inhibitor RAD001 (everolimus) in nasopharyngeal carcinoma and cisplatin-resistant cell lines. Invest New Drugs. 2010;28:413-20 pubmed publisher..AKT upregulation following RAD001 treatment suggests the presence of a feedback loop on AKT signaling in NPC which warrants further investigation. ..
- Hegner B, Lange M, Kusch A, Essin K, Sezer O, Schulze Lohoff E, et al. mTOR regulates vascular smooth muscle cell differentiation from human bone marrow-derived mesenchymal progenitors. Arterioscler Thromb Vasc Biol. 2009;29:232-8 pubmed publisher..We describe novel pleiotropic effects of rapamycin at very low concentrations that stabilized differentiated contractile VSMCs from MSCs in addition to exerting antiproliferative and enhanced homing effects. ..
- Richter J, Klann E. Making synaptic plasticity and memory last: mechanisms of translational regulation. Genes Dev. 2009;23:1-11 pubmed publisher..Here, we review recent studies that reflect the importance and challenges of investigating the role of mRNA translation in synaptic plasticity and memory formation. ..