Search results for "P70-S6 Kinase 1"
showing 10 items of 11 documents
The Intracellular Cleavage Product of the NG2 Proteoglycan Modulates Translation and Cell-Cycle Kinetics via Effects on mTORC1/FMRP Signaling
2018
The NG2 proteoglycan is expressed by oligodendrocyte precursor cells (OPCs) and is abundantly expressed by tumors such as melanoma and glioblastoma. Functions of NG2 include an influence on proliferation, migration and neuromodulation. Similar to other type-1 membrane proteins, NG2 undergoes proteolysis, generating a large ectodomain, a C-terminal fragment (CTF) and an intracellular domain (ICD) via sequential action of α- and γ-secretases which is enhanced by neuronal activity. Functional roles of NG2 have so far been shown for the full-length protein, the released ectodomain and CTF, but not for the ICD. In this study, we characterized the role of the NG2 ICD in OPC and Human Embryonic Ki…
Phosphoproteomics of the developing heart identifies PERM1 - An outer mitochondrial membrane protein.
2021
Heart development relies on PTMs that control cardiomyocyte proliferation, differentiation and cardiac morphogenesis. We generated a map of phosphorylation sites during the early stages of cardiac postnatal development in mice; we quantified over 10,000 phosphorylation sites and 5000 proteins that were assigned to different pathways. Analysis of mitochondrial proteins led to the identification of PGC-1- and ERR-induced regulator in muscle 1 (PERM1), which is specifically expressed in skeletal muscle and heart tissue and associates with the outer mitochondrial membrane. We demonstrate PERM1 is subject to rapid changes mediated by the UPS through phosphorylation of its PEST motif by casein ki…
Identification of a Novel Pathway in BCR/ABL Signal Transduction Involving Akt-Independent Activation of PLC-gamma/mTOR/p70-S6K.
2006
Abstract In BCR/ABL positive CML, defining new, additional therapeutic targets in the pathways, activated by BCR/ABL is critical for the development of new treatment strategies, especially for patients resistant or refractory to Imatinib. While studying the involvement of PI3K/Akt/mTOR signaling pathway in the development of such resistance we have uncovered the existence of additional, Akt-independent mechanism of activation of mTOR/p70-S6 Kinase pathway. Short term treatment with Imatinib (1μM, 4 hours) of the BCR/ABL-positive cell lines LAMA84, AR320, KCL22, K562, Ba/F3-BCR/ABL caused downregulation of p70-S6K phosphorylation and of S6 ribosomal protein phosphorylation without decreasing…
Molecular signaling in muscle is affected by the specificity of resistance exercise protocol
2010
Mammalian target of rapamycin and mitogen-activated protein kinase (MAPK) signaling pathways have been highlighted as important for muscle adaptations and thus, they may distinguish adaptations to different exercises. Typically, resistance exercise designed for muscle hypertrophy has moderate intensity (60-80% of one repetition maximum, 1 RM) while one prioritizing maximal strength with minor hypertrophy has a higher intensity (≥90% of 1 RM). Eight untrained men (28.4 ± 3.7 years) conducted two different bilateral leg press exercise protocols: hypertrophic (5 × 10 RM) and pure maximal strength (15 × 1 RM) in a counterbalanced, cross-over design with 1 week between exercises. Vastus laterali…
Resistance exercise with whey protein ingestion affects mTOR signaling pathway and myostatin in men.
2009
Signaling pathways sense local and systemic signals and regulate muscle hypertrophy. The effects of whey protein ingestion on acute and long-term signaling responses of resistance exercise are not well known. Previously untrained young men were randomized into protein ( n = 9), placebo ( n = 9), and control ( n = 11) groups. Vastus lateralis (VL) muscle biopsies were taken before and 1 h and 48 h after a leg press of 5 × 10 repetitions [resistance exercise (RE)] and after 21 wk (2 times per week) of resistance training (RT). Protein (15 g of whey) or nonenergetic placebo was ingested before and after a single RE bout and each RE workout throughout the RT. The protein group increased its bo…
Altered REDD1, myostatin, and Akt/mTOR/FoxO/MAPK signaling in streptozotocin-induced diabetic muscle atrophy
2011
Type 1 diabetes, if poorly controlled, leads to skeletal muscle atrophy, decreasing the quality of life. We aimed to search highly responsive genes in diabetic muscle atrophy in a common diabetes model and to further characterize associated signaling pathways. Mice were killed 1, 3, or 5 wk after streptozotocin or control. Gene expression of calf muscles was analyzed using microarray and protein signaling with Western blotting. We identified translational repressor protein REDD1 (regulated in development and DNA damage responses) that increased seven- to eightfold and was associated with muscle atrophy in diabetes. The diabetes-induced increase in REDD1 was confirmed at the protein level. …
Muscle protein synthesis, mTORC1/MAPK/Hippo signaling, and capillary density are altered by blocking of myostatin and activins
2012
Loss of muscle mass and function occurs in various diseases. Myostatin blocking can attenuate muscle loss, but downstream signaling is not well known. Therefore, to elucidate associated signaling pathways, we used the soluble activin receptor IIb (sActRIIB-Fc) to block myostatin and activins in mice. Within 2 wk, the treatment rapidly increased muscle size as expected but decreased capillary density per area. sActRIIB-Fc increased muscle protein synthesis 1–2 days after the treatment correlating with enhanced mTORC1 signaling (phosphorylated rpS6 and S6K1, r = 0.8). Concurrently, increased REDD1 and eIF2Bε protein contents and phosphorylation of 4E-BP1 and AMPK was observed. In contrast, pr…
Cannabinoid receptor 1 and acute resistance exercise – In vivo and in vitro studies in human skeletal muscle
2015
Abstract Aim This study aimed to determine whether Cannabinoid receptor 1 (CB1) is involved in mammalian target of rapamycin (mTOR) signaling and skeletal muscle protein synthesis. Methods This study used human vastus lateralis skeletal muscle biopsies obtained before and after a resistance exercise (RE) bout in young men (n = 18). The signaling mechanisms were studied in vitro in human myotubes. Protein expression was determined by Western blot and confocal microscopy, and gene expression by quantitative PCR. Protein synthesis was measured in vitro using puromycin-based SuNSET technique. Results In human skeletal muscle, an anabolic stimulus in the form of RE down-regulated CB1 expression.…
Docosahexaenoic acid protects human RPE cells against oxidative stress via PI3K/Akt m-TOR/p70-p85S6K pathways
2012
Purpose Oxidative Stress (OS) plays a critical role in the pathogenesis of age-related macular degeneration (AMD), especially by targeting the retinal pigment epithelium (RPE). Dietary habits with high consumption of docosahexaenoic acid (DHA) have been shown to prevent the development and evolution of AMD. Nevertheless, it is still unclear how DHA affects AMD. Our study aimed to investigate the involvement of the PI3K/Akt and m-TOR/p70-p85S6K pathways in human RPE cells after induction of OS, and then to assess the effect of DHA in the signaling pathways and in the protection against RPE cell death. Methods For this purpose, we used ARPE-19 cells exposed to the prooxidant agent, tert-butyl…
Down-Regulation of Ku Autoantigen, DNA-Dependent Protein Kinase, and Poly(ADP-ribose) Polymerase during Cellular Senescence
1997
During aging and cellular senescence mutations accumulate in genomic and mitochondrial DNA. Ku autoantigens, DNA-dependent protein kinase, and poly (ADP-ribose) polymerase have an essential role in DNA damage recognition. Our purpose was to find out whether cellular senescence of fibroblasts affects the protein components that recognize DNA damage and induce the repair process. We compared presenescent and replicatively senescent human WI-38 fibroblasts with each other and with SV-40 immortalized and serum-deficient quiescent WI-38 cells. Our results showed that replicative senescence significantly decreased the nuclear level of both p70 and p86 components of Ku autoantigen. SV-40 immortali…