Catalytic domain of the Protein Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase. Serine/Threonine Kinases (STKs), 70 kDa ribosomal protein S6 kinase (p70S6K) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The p70S6K subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate ...
90-kDa Ribosomal Protein S6 Kinases: A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.
Hypoxia inducible element-1α (HIF-1α) is an essential regulator of the cellular response to low oxygen concentrations activating a broad range of genes offering adaptive replies to air deprivation. suppresses the upstream signaling of HIF-1α such as for example PI3K/Akt/mTOR p42/p44 STAT3 and MAPK signaling under hypoxic circumstances. Furthermore we discovered that SA induces cell loss of life by stimulating G2/M cell routine arrest and apoptosis in individual colorectal cancers cells. Taken jointly SA was defined as a book little molecule HIF-1α inhibitor from sea natural products and it is potentially a respected candidate in the introduction of anticancer BMS-562247-01 realtors. sp. having anti-proliferative activity against several cancer tumor cells [16]. SA was defined as the initial supplementary metabolite from a saltern-derived actinomycetes microorganism as well as the initial chlorinated person in the manumycin family members. Nevertheless theres RP11-175B12.2 been no survey ...
癫痫是一种以反复发作的痉挛为特点的严重的神经系统疾病。它是由多种原因导致的,主要有遗传因素、脑损伤及环境因素,但是具体发病机制还不清楚。遗传性癫痫家族研究发现癫痫是由一些编码离子通道以及神经递质受体蛋白的基因突变导致的。随着技术进步和研究深入,逐渐发现癫痫遗传不仅由离子通道和神经递质基因控制,还受突触小泡转运通路,染色质重塑和转录,mTOR蛋白信号通路等相关基因,染色体拷贝数变异及表观遗传学的影响。该文主要讨论癫痫相关基因、染色体异常和表观遗传学对癫痫发生的影响。
We show here that STAT5 is essential for sustained activation of the Akt/p70S6K pathway, which was previously thought to be an exclusive function of Shc. At early time points after IL-2 stimulation, our results are consistent with the conventional model in which a complex containing Shc, Grb2, Gab2, Shp2, and p85 mediates activation of the Akt/p70S6K pathway (14, 15, 16). However, when concurrent STAT5 activity was absent, the Akt/p70S6K signal waned after 3-6 h of IL-2 stimulation, and this was associated with drastically impaired lymphocyte proliferation and viability. Restoration of STAT5 activity through a heterologous receptor rescued maximal Akt/p70S6K activity and lymphocyte proliferation. The Shc pathway further promoted these events by enhancing the transcriptional activity of STAT5. This bidirectional, cooperative signaling by Shc and STAT5 appears to operate throughout the proliferative cycle, as temporal dissociation of the Shc and STAT5 signals lead to suboptimal S6 phosphorylation ...
BioAssay record AID 460031 submitted by ChEMBL: Inhibition of mTOR TORC1 kinase activity in human MDA-MB-361 cells assessed as suppression of p70S6K phosphorylation at < 30 nM.
Immunhistochemische Untersuchungen zur lokoregionären Verteilung von mTOR, p-mTOR und 4E-binding protein im Prostataraum tumortragender Prostaten mittels der Tissue Microarray- ...
BEZ235 (NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM, respectively. Inhibits ATR with IC50 of 21 nM, whileshown to be a poor inhibitor to Akt and PDK1. Phase 2. ...
antibodies associated with mammalian target of rapamycin (mTOR) in signal transduction. - All Product Showcase - Products - Abnova
Further evaluation of PI3K/AKT/mTOR pathway inhibitors is required to confirm whether the patterns of sensitivity observed in preclinical studies can be applied in the clinic. Although many early-phase trials have independently failed to identify a distinct association between clinical response and the most common alterations in the PI3K pathway (PIK3CA mutation and PTEN loss), a pooled analysis of 140 patients with various breast and gynecologic cancers treated with different PI3K/AKT/mTOR inhibitors identified an increased rate of RECIST-defined clinical responses among patients with PIK3CA mutations (75). A follow-up study pooling 1,012 patients with diverse cancers treated with PI3K/AKT/mTOR pathway inhibitors also identified an increased rate of response among tumors with PIK3CA H1047R mutation, but not those with other PIK3CA mutations or concurrent PIK3CA and KRAS mutations (76). The findings of these association studies have sparked interest in the research community; however, additional ...
Studies have demonstrated the role mechanical stress plays in regulating osteoblastic functions, such as cellular proliferation, osteogenic differentiation, signal transduction and apoptosis (14-16,26). Energy metabolism is essential to maintaining the biological activities of osteoblasts (17). In the present study, we revealed a novel mechanism in osteoblastic mechanobiology, through which cyclic stretch promotes osteoblastic energy metabolism by increasing the expression of enzymes associated with energy metabolism, partially through the Akt/mTOR/p70s6k signaling pathway. Firstly, cyclic mechanical stretch promoted energy metabolism in the MG-63 cells, which was evidenced by the increased glucose consumption, and the increased levels of lactate, intracellular ATP, and energy metabolism-related genes (ATP5B, ATP5F1, ATP5J, F1-ATPase α, LDHA and enolase 1), and ATP5B and ATP5J proteins. Secondly, cyclic mechanical stretch stimulated the activation of the Akt/mTOR/p70s6k pathway by prompting the ...
The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. Therefore, it is directly related to cellular quiescence, proliferation, cancer, and longevity. PI3K activation phosphorylates and activates AKT, localizing it in the plasma membrane. AKT can have a number of downstream effects such as activating CREB, inhibiting p27, localizing FOXO in the cytoplasm, activating PtdIns-3ps, and activating mTOR which can affect transcription of p70 or 4EBP1. There are many known factors that enhance the PI3K/AKT pathway including EGF, shh, IGF-1, insulin, and CaM. The pathway is antagonized by various factors including PTEN, GSK3B, and HB9. In many cancers, this pathway is overactive, thus reducing apoptosis and allowing proliferation. This pathway is necessary, however, to promote growth and proliferation over differentiation of adult stem cells, neural stem cells specifically. It is the difficulty in finding an appropriate amount of proliferation versus ...
FERREIRA, MGPA et al. The importance of the PI3K/AKT/mTOR signaling pathway in canine neoplasms: Literature review. Arch. med. vet. [online]. 2016, vol.48, n.2, pp.139-143. ISSN 0301-732X. http://dx.doi.org/10.4067/S0301-732X2016000200002.. The PI3K/AKT/mTOR pathway is related to proliferation, protein synthesis, survival, angiogenesis, apoptosis, and cell motility. Genetic alterations in either activation of oncogenes or inactivation of tumor suppressor make it the second most altered pathway in neoplastic processes. The PI3K/AKT/mTOR pathway is currently considered an attractive target for the development of anti-tumor molecules. Specific inhibitors of this pathway are under development, and those already recognized are being tested in clinical trials, representing a promising approach for the treatment of cancer patients. It is believed that, as this pathway is involved in the development of many human cancers, its activation may also be related to the development of various canine neoplasms. ...
Clinical trial design. The success of tyrosine kinase inhibitors, such as erlotinib and imatinib, and the strong rationale to target the PI3K/Akt/mTOR pathway has fed optimism that inhibitors of serine/threonine kinases, such as PI3K, PDK-1, Akt, or mTOR, might have clinical use for cancer patients. Because these drugs are predicted to modulate a target and do not cause direct DNA damage like most standard chemotherapies, the design of clinical trials with PI3K/Akt/mTOR pathway inhibitors should reflect their biological activities. Based on numerous preclinical studies, pathway inhibitors are likely to be most effective in patients whose tumors bear activation of the pathway. Thus, phase I protocols with inhibitors of the PI3K/Akt/mTOR pathway should determine the biologically effective dose and the maximum tolerated dose and should determine the relationship between these doses. Although it can be argued that determining a tolerated biologically effective dose is sufficient for a targeted ...
The phosphatidylinositol-3-kinase /protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway plays an important role in cell proliferation, growth, and angiogenesis.
mTOR/S6 kinase pathway contributes to astrocyte survival during ischemia. - María Dolores Pastor, Isaac García-Yébenes, Noelia Fradejas, José Manuel Pérez-Ortiz, Silvia Mora-Lee, Pedro Tranque, María Angeles Moro, Mario Pende, Soledad Calvo
... , AS16 3832, Q2F981; LOC_Osm1g00310.1, Ribosomal protein small subunit 2.
... , AS16 3835, Q2F963; LOC_Osm1g00500.1, Ribosomal protein small subunit 1.
Background: Mammalian target of rapamycin (mTOR) inhibitors are found in a variety of malignancies. (CI 95%, 1.54C4.41, control (RR=1.97; 95% CI, 0.97C4.03, all other malignancies. The RR of all-grade contamination in patients treated with RCC was 1.84 (95% CI, 1.53C2.21; phase III trials. There were no statistically significant differences between the phase subgroups for either grade (all-grade 33.1% Motzer et al, 2010), the RECORD-1 Study Group subsequently published recommendations for the management of infections and other adverse events according to the grade buy Lafutidine of the event (Porta et al, 2011; Ravaud, 2011). These recommendations can be used by clinicians to effectively manage treatment-related infections. Fungal infections such as Candida and Aspergillosis, mycobacterial infections such as tuberculosis, and viral infections such as hepatitis and herpes occurred in the studies used in our analysis and were reported in the prescribing information (Novartis, 2012; Pfizer, 2012). ...
Rapamycin derivatives selected among 32(S)-dihydro-rapamycin derivatives and 32-deoxo-rapamycin compounds. Rapamycin derivatives are disclosed of the formula: ##STR1## wherein the variables are in the specification.
One more rising problem is that Kendall Reyes Chargers Jersey , in addition to im pting the advancent and survival of aberrant cells, CR and mTOR inhibition
90 kDa ribosomal protein S6 kinase 1; HU-1; MAP kinase-activated protein kinase 1a; MAPK-activated protein kinase 1a; MAPKAP kinase 1a; MAPKAPK-1a; MAPKAPK1A; RSK; RSK-1; RSK1; S6K-alpha 1; S6K-alpha-1; dJ590P13.1 (ribosomal protein S6 kinase, 90kD, polypeptide 1); p90-RSK 1; p90RSK1; p90S6K; ribosomal S6 kinase 1; ribosomal protein S6 kinase alpha 1; ribosomal protein S6 kinase alpha-1; ribosomal protein S6 kinase, 90kD, polypeptide 1; ribosomal protein S6 kinase, 90kDa, polypeptide ...
Catalpol induces cell activity to promote axonal regeneration via the PI3K/AKT/mTOR pathway in vivo and in vitro stroke model
The potential role of AKT/mTOR signalling proteins and its association with the Raf-MEK-ERK pathway was investigated in hairy cell leukaemia (HCL). BRAFV600E expression and activated forms of AKT, mTOR, ERK1/2, p70S6k and 4E-BP1 were immunohistochemically assessed in 77 BM biopsies of HCL patients and correlated with clinicopathological and BM microvascular characteristics, as well as with c-Caspase-3 levels in hairy cells. Additionally, we tested rapamycin treatment response of BONNA-12 wild-type cells or transfected with BRAFV600E. Most HCL cases expressed p-p70S6K and p-4E-BP1 but not p-mTOR, being accompanied by p-ERK1/2 and p-AKT. AKT/mTOR activation was evident in BONNA-12 cells irrespective of the presence of BRAFV600E mutation and was implicated in cell proliferation enhancement. In multivariate analysis p-AKT/p-mTOR/p-4E-BP1 overexpression was an adverse prognostic factor for time to next treatment conferring earlier relapse. When p-AKT, p-mTOR and p-4E-BP1 were examined separately only p-4E
The mTOR signaling pathway plays a central role in cell growth and survival control (Laplante & Sabatini, 2012). Therefore, it is not surprising that several stress conditions regulate mTOR activity, thereby allowing cells to survive under non‐optimal conditions (Sengupta et al, 2010). In particular, it has been demonstrated that the tumor suppressor p53 upon several kinds of stress can repress mTOR through multiple mechanisms (Ellisen et al, 2002; Feng et al, 2007; Budanov & Karin, 2008).. In the present study, we provide evidence that Che‐1 negatively controls mTOR activity in a p53‐independent way, consequently requiring TSC2. We show that Che‐1 is activated by several stress conditions and inhibits mTOR pathway by inducing Redd1 and Deptor expression, two important inhibitors of mTOR. Furthermore, inhibition of Che‐1 strongly decreases autophagy leading to apoptosis. We also document overexpression of Che‐1 during MM progression and a positive correlation between Che‐1 and ...
Purpose:EGFR overexpression is correlated with decreased survival in head and neck cancer (HNC) where the addition of EGFR inhibition to standard chemoradiation approaches has improved treatment responses. However, the basis for the limited efficacy of EGFR inhibitors in HNC is incompletely understood. G-protein-coupled receptors (GPCRs) have been shown to be overexpressed in HNC where GPCR activation induces HNC growth via both EGFR-dependent and independent pathways. We hypothesized that targeting GPCR-induced EGFR-independent signaling would improve the efficacy of EGFR inhibition. Experimental Design:Using a high-throughput phospho-proteome array, we identified proteins that were phosphorylated in HNC cells where EGFR expression was downmodulated by RNAi in the presence or absence of a GPCR ligand. We confirmed the findings from the array by Western blotting followed by in vitro and in vivo phenotypic assays. Results:p70S6K phosphorylation was elevated approximately 6-fold in EGFR siRNA ...
A protein that helps control several cell functions, including cell division and survival, and binds to rapamycin and other drugs. Mammalian target of rapamycin may be more active in some types of cancer cells than it is in normal cells.
The Lamming laboratory is primarily focused on understanding the physiological role played by the mechanistic target of rapamycin (mTOR), a protein kinase that, through a diverse set of substrates, regulates cellular processes including growth, metabolism, and aging. Recent work hasshown that rapamycin, an inhibitor of mTOR signaling, can promote health and longevity in model organisms including mammals. As detailed by Dr. Lamming in a recent review article - Rapalogs and mTOR inhibitors as anti-aging therapeutics - understanding and manipulating the mTOR signaling pathway may provide insight into the treatment of age-related diseases, including diabetes, Alzheimers disease, and cancer.. ...
The 70kDa ribosomal protein S6 kinases (S6K1 and S6K2) play important roles in the regulation of protein synthesis, cell growth and survival. S6Ks are activated in response to mitogen stimulation and nutrient sufficiency by the phosphorylation of conserved serine and threonine residues. Here we show for the first time, that in addition to phosphorylation, S6Ks are also targeted by lysine acetylation. Following mitogen stimulation, S6Ks interact with the p300 and p300/CBP-associated factor (PCAF) acetyltransferases. S6Ks can be acetylated by p300 and PCAF in vitro and S6K acetylation is detected in cells expressing p300. Furthermore, it appears that the acetylation sites targeted by p300 lie within the divergent C-terminal regulatory domains of both S6K1 and S6K2. Acetylation of S6K1 and 2 is increased upon the inhibition of class I/II histone deacetylases (HDACs) by trichostatin-A, while the enhancement of S6K1 acetylation by nicotinamide suggests the additional involvement of sirtuin ...
Title:A Marine-based Meriolin (3-Pyrimidinylazaindole) Derivative (4ab) Targets PI3K/AKT /mTOR Pathway Inducing Cell Cycle Arrest and Apoptosis in Molt-4 Cells VOLUME: 6 ISSUE: 1. Author(s):Gousia Chashoo*, Umed Singh, Parvinder P. Singh, Dilip M. Mondhe and Ram A. Vishwakarma. Affiliation:Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Academy of Scientific and Innovative Research, Canal Road, Jammu, Jammu & Kashmir-180001, Department of Chemistry, Guru Jambheshwar University of Science and Technology, Hisar, Haryana, Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Academy of Scientific and Innovative Research, Canal Road, Jammu, Jammu & Kashmir-180001, Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Academy of Scientific and Innovative Research, Canal Road, Jammu, Jammu & Kashmir-180001, Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Academy of Scientific and Innovative ...
We propose here that blunted AKT/mTOR signaling and cellular metabolism is a mechanism by which high salt reduces M(IL-4+IL-13) activation. AKT was recently shown to be important in synergizing with STAT6 signaling to acquire complete M(IL-4) activation (37). In their study, the attenuation of AKT signaling, either by genetic modulation or chemical inhibition, resulted in an impaired M(IL-4) activation, independent of an effect on STAT6 phosphorylation (37). Byles et al. additionally identified a regulatory loop between AKT/mTOR upon stimulation of macrophages with IL-4 (37). In support of this, we additionally observed impaired activation of a downstream target of AKT, mTOR (p70S6K). Furthermore, with constitutive active AKT signaling, we were able to rescue the effect of NaCl on reducing M(IL-4+IL-13) gene expression.. Since AKT/mTOR is known to regulate cellular responses to changes in nutrient and energy availability, we hypothesized that an outcome of this decreased signaling would be a ...
Ribosomal protein S6 kinase 1 (S6K1), a critical mediator of cell growth, is overexpressed in breast cancer and is associated with poor prognosis. S6K1 has two known isoforms, p85(S6K1) and p70(S6K1). p85(S6K1) is characterized by 23 additional amino acids in the N-terminus of p70(S6K1). This is tho …
The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth and proliferation that is often aberrantly activated in cancer, as...
PDCD11小鼠单克隆抗体[158C1a](ab84852)可与重组片段样本反应并经WB实验严格验证。中国75%以上现货,所有产品均提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
Despite improvement in preoperative imaging, surgical technique, and adjuvant therapy, the prognosis of patients with tongue squamous cell carcinoma (SCC) is still unsatisfactory. The mammalian target of rapamycin (mTOR) play a key role in the regulation of tumor cell proliferation and survival. However, the significance of mTOR on the prognosis of tongue SCC remains largely undefined. In the present study, immunohistochemistry was performed to evaluate the expression of phosphorylated mTOR (p-mTOR) in 160 surgically resected tongue SCC, and correlated with survival. Univariate analysis revealed that p-mTOR overexpression (P = 0.006) was associated with inferior overall survival. In multivariate comparison, p-mTOR overexpression (P = 0.002, hazard ratio = 2.082) remained independently associated with worse overall survival. In vitro study, tongue cancer cells treated with everolimus, the specific mTOR inhibitor, or transfected with mTOR-mediated siRNAs dramatically attenuated the abilities of ...
Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and its derivative, everolimus, are potent immunosuppressive and antiproliferative drugs. Inflammatory diseases are characterized by immunological dysfunction, and monocyte recruitment underlies the mechanism of cell damage. Chemokines attract inflammatory cells to sites of inflammation. Interleukin-8 (IL-8/CXCL8); the monocyte chemoattractant protein-1 (MCP-1/CCL2); the regulated on activation, normal T cell expressed, presumably secreted protein (RANTES/CCL5); the macrophage inflammatory protein (MIP)-1α (CCL3); and MIP-1β (CCL4) are involved in the pathogenesis of inflammation. However, whether mTOR inhibitors moderate the production of chemokines in monocytes remains unclear. A human monocyte cell line, THP-1, and primary monocytes obtained from human volunteers, were stimulated using lipopolysaccharide (LPS), and then treated with sirolimus. The expression of the MCP-1, RANTES, IL-8, MIP-1α, MIP-1β, and TNF-α proteins was
Regulatory associated protein of mTOR, complex 1 (Raptor) is encoded by the RPTOR gene. It is involved in the control of the mammalian target of rapamycin (mTOR) and is a subunit of mTORC1. Raptor binds to mTOR kinase and functions as a scaffold for recruiting mTORC1 substrates. It also associates with eukaryotic translation initiation factor 4E-binding protein 1 (EIF4BP1) and ribosomal protein S6 kinase (S6K1). Raptor negatively regulates mTOR kinase but positively regulates S6K1. Raptor also interacts with unc-51-like kinase 1 (ULK1) in a nutrient-dependent manner. Raptor is also known as p150 target of rapamycin (TOR)-scaffold protein, KIAA1303, KOG1, and Mip1.. ...
Recombinant Ribosomal Protein S16 (RPS16) Protein (His tag). Species: Mouse (Murine). Source: Escherichia coli (E. coli). Order product ABIN3132967.
This proposal has two goals: contribute to our understanding of the biology of Tor signaling in the fungal opportunistic pathogen C. albicans, and identify pote...
Evermil 5mg is a derivative of Rapamycin (sirolimus) and works similarly to Rapamycin as an mTOR (mammalian target of rapamycin) inhibitor @ MHP
mTOR is recruited to lysosomal vacuoles harboring engulfed cells but not latex beads. (A) Top, mTOR (left) is recruited to corpse-containing entotic vacuole (ar