Loss of hydrophobic motif and activation loop phosphorylation is a consequence and not the mechanism of S6 kinase 1 inhibition by rapamycin.

Abstract:

:S6K1 regulation associates a central role with dynamics of sequential phosphorylations at the hydrophobic motif (T412) and activation loop (T252) of the enzyme, such that the hydrophobic motif phosphorylation supposedly brought about by mTOR- kinase, primes the enzyme for PDK1 dependent phosphorylation at the activation loop for its full activation. Accordingly loss of hydrophobic motif phosphorylation attributed to TOR- kinase inhibition, with resultant loss of activation loop phosphorylation is the hypothesis put forward to explain the mechanism of rapamycin inhibition. Our recent observation that rapamycin continues to inhibit S6K1 in the absence of either phosphorylation, together with the evidence that phosphorylation at activation loop may occur prior to that of hydrophobic motif raises serious questions about the proposed mechanism of rapamycin inhibition. Here, we show that rapamycin fails to effect preferential loss of either phosphorylation and the two instead exhibit equal sensitivity to rapamycin both in time and quantum. We further show that of activation loop and hydrophobic motif phosphorylations turnover in an interdependent manner so as to exhibit all or none pattern of loss to rapamycin. Using insect cell expression system, we further substantiate their interdependent turnover and provide evidence that the two phosphorylations are brought about in a coordinate and not sequential manner. These data together with the observation that both kinases that cause hydrophobic motif and activation loop phosphorylations in insect or mammalian cells are completely insensitive to inhibition by rapamycin, suggest that their loss is a consequence and not the mechanism of rapamycin inhibition in accordance with the model proposed herein.

authors

Beigh MA,Showkat M,Hussain MU,Andrabi KI

subject

Has Abstract

pub_date

2013-04-01 00:00:00

pages

399-408

issue

2

eissn

0393-974X

issn

1724-6083

pii

12

journal_volume

27

pub_type

杂志文章
  • Association between progesterone and estradiol-17beta treatment and protein expression of pgr and PGRMC1 in porcine luminal epithelial cells: a real-time cell proliferation approach.

    abstract::The correct functionality (sensitivity and receptivity) of endometrial tissue is regulated by paracrine and endocrine pathways that activate several mediators or metabolic pathways and gene cascades. This study aimed to investigate the influence of E2 and P4 on progesterone receptor (PGR) and progesterone receptor mem...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: Kempisty B,Wojtanowicz-Markiewicz K,Ziółkowska A,Budna J,Ciesiółka S,Piotrowska H,Bryja A,Antosik P,Bukowska D,Wollenhaupt K,Bruska M,Brüssow KP,Nowicki M,Zabel M

    更新日期:2015-01-01 00:00:00

  • Immune responses to tetanus vaccination in Italian healthy subjects and children with recurrent infections.

    abstract::The ability of vaccine antigen to generate protection is a challenge that cannot be restricted to the antibody response; however, the contribution of T cell-mediated mechanisms has not been extensively analyzed. Age and administration to specific categories of patients, i.e. children with recurrent infections (RI), ar...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: Graziani S,Romiti ML,Capponi C,Di Cesare S,Corrente S,Monteferrario E,Di Paolo A,De Marchis C,Chini L,Moschese V

    更新日期:2013-01-01 00:00:00

  • The BCR signalosome: where cell fate is decided.

    abstract::B cell antigen receptor (BCR) engagement results in the assembly of a multimolecular complex at the cytosolic side of the plasma membrane, known as signalosome. Here we briefly review the current knowledge on the molecules which participate in the BCR signalosome and on the response modulators which control the final ...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章,评审

    doi:

    authors: Ulivieri C,Baldari CT

    更新日期:2005-01-01 00:00:00

  • Restoration of the degenerated cervical intervertebral space: how much should we distract? A magnetic resonance imaging study.

    abstract::The aim of the study was to quantify normal cervical disc space measurements and to generate a normal values' database. Furthermore, during operative restoration of a degenerated intervertebral disc, it is difficult to calculate the amount of distraction required to restore the collapsed space to its normal height. A ...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: Fyllos AH,Zibis AH,Banios K,Mitrousias VD,Karantanas AH,Markou AS,Mangiavini L,Luceri F

    更新日期:2020-07-01 00:00:00

  • Balance between epithelial and stromal marker expression and distribution in primary culture model of porcine endometrium during real-time cell proliferation..

    abstract::The similarity between humans and pigs, when it comes to tissue morphology, makes Sus scrofa not only a good research model, but also a potential source of cells for tissue engineering. Cell samples obtained from the pig donor, could be influenced in vitro, in order to become a source of tissue material for xenotransp...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: Wojtanowicz-Markiewicz K,Nawrocki MJ,Brązert M,Ożegowska K,Jankowski M,Rojewska M,Kocherova I,Kulus M,Jeseta M,Bryja A,Porowski L,Bukowska D,Skowroński MT,Bręborowicz A,Bruska M,Zabel M,Nowicki M,Kempisty B,Antosik P

    更新日期:2018-09-01 00:00:00

  • Generalized eruptive histiocytoma in adult patient.

    abstract::Generalized eruptive histiocytoma is a rare benign skin disorder with less than 50 cases reported world-wide. It belongs to type IIb of histiocytoses. The histiocytic cells are CD68 positive but lack other markers like CD1a or S100. We report on a 60-year-old male patient with generalized eruptive histiocytoma treated...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: Hansel G,Schönlebe J,Tchernev G,Chokoeva AA,Lotti T,Wollina U

    更新日期:2015-01-01 00:00:00

  • Hard and soft tissue changes in the rehabilitation of the anterior maxilla with triangular shape neck implants: a retrospective clinical study with a one-year follow up.

    abstract::Aim of this retrospective study was to evaluate the one-year clinical and radiographic outcomes of implants with a triangular shaped neck inserted immediately after tooth extraction in esthetic zones. Patients in which immediate postextraction implants were placed and restored in the anterior maxilla, who underwent a ...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 信件

    doi:

    authors: DENTAL SUPPLEMENT.,D'Avenia F,Del Fabbro M,Karanxha L,Weinstein T,Corbella S,Fumagalli D,Francetti L,Taschieri S

    更新日期:2019-11-01 00:00:00

  • Early and late behavioral changes in sciatic nerve injury may be modulated by nerve growth factor and substance P in rats: a chronic constriction injury long-term evaluation.

    abstract::Chronic constriction injury (CCI) simulates the symptoms of chronic nerve compression, which is characterized by allodynia and hyperalgesia. Nerve growth factor (NGF) is released after nerve injury by immune and Schwann cells and transported in retrograde fashion to the dorsal root ganglion (DRG), resulting in increas...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: Da Silva JT,Evangelista BG,Venega RAG,Oliveira ME,Chacur M

    更新日期:2017-04-01 00:00:00

  • A novel CAD/CAM-based surgical template for mandibular osteoplasty and guided implant insertion.

    abstract::Bone shaping is often a necessary procedure prior to implant insertion in mandibular full-arch rehabilitations. Adopting guided surgery procedures is necessary to use two distinct templates: one for bone shaping, a second for guided implant insertion. The present report describes the case of a 60-year-old patient requ...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: Menchini Fabris GB,Gelpi F,Giammarinaro E,Velasco Ortega E,Marconcini S,Covani U

    更新日期:2017-04-01 00:00:00

  • Patient-reported quality of life after endoscopic surgery for pituitary lesions: a meta-analysis.

    abstract::Patient-reported outcomes are now considered as an important part of overall outcome assessment of a surgical intervention. The objective of the current study was to evaluate the patient-reported quality of life (QoL) of the subjects of endoscopic pituitary surgery. A literature search was carried out in several elect...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 信件,meta分析

    doi:

    authors: Wang CH,Zhu N

    更新日期:2018-09-01 00:00:00

  • Inhibition of the differentiation of 3T3-L1 cells by interferon-beta and difluoromethyl ornithine.

    abstract::Both mouse interferon-beta (MuIFN-beta) and the inhibitor of ornithine decarboxylase (ODC), alpha-difluoromethyl ornithine (DFMO), inhibited the differentiation of mouse 3T3-L1 fibroblasts into adipocytes in a dose-dependent manner. DFMO and MuIFN-beta added together to cultures that were induced to differentiate prod...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: Taylor JL,Turo KA,McCann PP,Grossberg SE

    更新日期:1988-01-01 00:00:00

  • Mast cell and cancer with special emphasis on il-37 an anti-inflammatory and inhibitor of innate immunity: new frontiers.

    abstract::Mast cells (MCs) are mediators of allergy and inflammation and participate in the growth of cancer cells. MCs can promote both neoangiogenesis and tumor growth. They increase in the stroma of certain tumors where they can be recruited by tumor-derived chemoattractants, such as monocyte chemotactic protein-1 (MCP-1), R...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 社论

    doi:

    authors: Carinci F,Lessiani G,Spinas E,Kritas SK,Ronconi G,Caraffa Al,Conti P

    更新日期:2016-10-01 00:00:00

  • Residual mobility after removal of instrumentation in patient, with type a2-a3 vertebral fractures, treated with percutaneous pedicle screw fixation.

    abstract::Percutaneous techniques for treatment of thoraco-lumbar fractures type A2 and A3 are widely used. These techniques are considered temporary fixations and instrumentation must be removed with fracture healing. The aim of the study is to analyze clinical results, motility of treated segments and any loss of correction a...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: XIX CONGRESSO NAZIONALE S.I.C.O.O.P. SOCIETA' ITALIANA CHIRURGHI ORTOPEDICI DELL'OSPEDALITA' PRIVATA ACCREDITATA.,Proietti L,Perna A,Schirò GR,Noia G,Fumo C,Tamburrelli FC

    更新日期:2019-03-01 00:00:00

  • Impact of Sjögren's syndrome on oral health and quality of life: an observational cross-sectional study.

    abstract::Sjögren's Syndrome is a complex disease, due to an autoimmune physiopathology, that strongly impacts both patients' primary needs (nutrition and speaking), and patients' relationship life related factors (psychological health and quality of life). In Literature, few studies had investigated oral health status in Sjögr...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: DENTAL SUPPLEMENT.,Giuca MR,Miceli M,Carli E,Lardani L,Marchio V,Baldini C

    更新日期:2020-05-01 00:00:00

  • The comparison between vitamin d concentration in upper silesia patients with prostate cancer and with benign prostatic hyperplasia.

    abstract::A number of studies have shown that vitamin D has a protective effect against the development of cancer, which may also be related to prostate cancer. Low serum vitamin D concentration has also been demonstrated in benign prostate hyperplasia. We compared serum vitamin D concentration in two groups of Polish men with ...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 信件

    doi:

    authors: Wieczorek K,Braczkowski RS,Skrzypek M,Stryjewski PJ,Kuczaj A,Al-Srory G

    更新日期:2015-01-01 00:00:00

  • Effect of tannin extract against Pseudomonas aeruginosa producing metallo beta-lactamase.

    abstract::Carbapenems are the most potent beta-lactam agents with a broad-spectrum activity against Gram-negative and Gram-positive bacteria. They are stable in the presence of penicillinases and cephalosporinases. This study was focused on frequency of metallo beta- lactamase (MBL) among Pesudomonas aeruginosa strains isolated...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: Ghafourian S,Mohebi R,Sekawi Z,Raftari M,Neela V,Ghafourian E,Aboualigalehdari E,Rahbar M,Sadeghifard N

    更新日期:2012-04-01 00:00:00

  • Human T lymphocyte cell line (Mo) and its subclone (J) produce colony stimulating activity on normal and malignant T cell precursors.

    abstract::Conditioned medium from a T-lymphoblastic cell line (Mo) is known to produce factors promoting CFU-GM, BFU-E and CFU-MK. In our study we investigated the potential CSA of conditioned media obtained from Mo and its subclone J on normal and malignant lymphoid progenitors of both T and B lineage. Both cell lines release ...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: Legitimo A,Consolini R,Bason C,Balleari E,Macchia P

    更新日期:1995-10-01 00:00:00

  • Hemodialysis in children: how, when and why.

    abstract::End-stage renal diseases requiring chronic dialysis are rare in childhood and adolescence, but they are associated with high mortality and impaired quality of life (1, 2). The most common disease that causes chronic kidney disease (CKD) is primary glomerular disease (GD), followed by congenital abnormalities of the ki...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 临床试验

    doi:

    authors: special issue: “Focus on pediatric nephrology”.,Chimenz R,Fede C,Di Benedetto V,Concolino D,Scuderi MG,Salvo V,Gitto E,Cucinotta U,Viola V,Betta P,Cannavò L,Cuppari C

    更新日期:2019-09-01 00:00:00

  • IL-32: a newly-discovered proinflammatory cytokine.

    abstract::IL-32, a newly-discovered proinflammatory cytokine that activates the p38MAPK and NF-kappaB pathways, is an important player in innate and adaptive immune response. IL-32, a cytokine produced mainly by T, natural killer, and epithelial cells induces significant amounts of TNFalpha and MIP-2 and increases the productio...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 社论,评审

    doi:

    authors: Felaco P,Castellani ML,De Lutiis MA,Felaco M,Pandolfi F,Salini V,De Amicis D,Vecchiet J,Tete S,Ciampoli C,Conti F,Cerulli G,Caraffa A,Antinolfi P,Cuccurullo C,Perrella A,Theoharides TC,Conti P,Toniato E,Kempuraj D,

    更新日期:2009-07-01 00:00:00

  • Periodontitis and cerebrovascular disease: a new novel in medicine.

    abstract::The aim of this review is to determine if there is a relationship between periodontal disease and stroke. The included case-control and cohort studies mediate the incidence of stroke and periodontal disease by analyzing different parameters. A literature review was carried out in PubMed, Scopus and Embase databases us...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章,评审

    doi:

    authors: DENTAL SUPPLEMENT.,Campanella V,Oberti L,Gabrione F,González-Valero L,Hernández-Martínez V,Silvestre-Rangil J

    更新日期:2019-05-01 00:00:00

  • Transcriptional profile characterization for the identification of peripheral blood biomarkers in patients with cerebral aneurysms.

    abstract::We tried to identify molecular markers in peripheral blood to predict high risk of aneurysm rupture. Extraction of the total population of peripheral blood mononuclear cell (PBMC) from total blood volume, total RNA extraction from PBMC and Agilent One Color Gene-expression Oligo-Microarray were performed on peripheral...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: Sabatino G,Rigante L,Minella D,Novelli G,Della Pepa GM,Esposito G,Albanese A,Maira G,Marchese E

    更新日期:2013-07-01 00:00:00

  • Relationship between sleep/wakefulness and gastroesophageal reflux in symptomatic newborns.

    abstract::The state of sleep/wakefulness is well known to influence esophageal acid exposure and the number of acid refluxes whereas it is uncertain whether the same is true of the non-acid refluxes that predominate in the newborns. To investigate the relationship between sleep/wakefulness and refluxes 45 newborns with gastroes...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: Cresi F,Locatelli E,Maggiora E,Di Nicola P,Cester E,Sabatino G,Martano C,Giuliani F,Bertino E

    更新日期:2012-07-01 00:00:00

  • Regulatory effect of miRNA on multi-directional differentiation ability of mesenchymal stem cell in treatment of osteoporosis.

    abstract::This study was designed to evaluate the effect of miRNA acting in regulating multi-directional differentiation ability of mesenchymal stem cell in treatment of osteoporosis (OP), with the aim of finding a new idea and approach for clinical treatment of OP. Estrogen deficiency-induced OP mice model was established by m...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: Teng ZW,Zhu Y,Na Q,Zhang XG,Zhao H,Wei GJ,Zhao J,Zhang XW,Wang GZ,Liang J,Zhang ZJ,Liu YG

    更新日期:2016-04-01 00:00:00

  • Pain reduction and improvement of function following ultrasound-guided intra-articular injections of triamcinolone hexacetonide and hyaluronic acid in hip osteoarthritis.

    abstract::The scientific literature has shown positive results regarding intra-articular injections of hyaluronic acid in osteoarthritic joints. When injecting in the hip joint, the guidance of ultrasound can provide higher injection accuracy and repeatability. However, due to the methodological limitations in the current avail...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: Araújo JP,Silva L,Andrade R,Paços M,Moreira H,Migueis N,Pereira R,Sarmento A,Pereira H,Loureiro N,Espregueira-Mendes J

    更新日期:2016-10-01 00:00:00

  • Flake size-dependent cyto and genotoxic evaluation of graphene oxide on in vitro A549, CaCo2 and vero cell lines.

    abstract::This study was carried out by varying both graphene oxide (GO) concentration (10 μg/mL, 50 μg/mL, 100 μg/mL) and flakes sizes of 1320 nm and 130 nm. Characterization by scanning electron microscopy and Raman spectroscopy demonstrate that the area of GO flakes varies of one order of magnitude but their c...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: De Marzi L,Ottaviano L,Perrozzi F,Nardone M,Santucci S,De Lapuente J,Borras M,Treossi E,Palermo V,Poma A

    更新日期:2014-04-01 00:00:00

  • Sublingual immunotherapy provides an early increase of interferon-gamma production.

    abstract::Allergic rhinitis (AR) is characterized by Th2 polarized immune response. Allergen-specific subcutaneous immunotherapy may restore a physiologic Th1 profile. However, there are few studies investigating the immunological effects of sublingual immunotherapy (SLIT). The aim of this study is to investigate whether a pre-...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 临床试验,杂志文章

    doi:

    authors: Ciprandi G,Fenoglio D,Di Gioacchino M,Ferrera A,Ferrera F,Sormani MP,Marseglia GL

    更新日期:2008-07-01 00:00:00

  • Intravenous IgG: biological modulating molecules.

    abstract::Intravenous IgG has been adopted as treatment for various immune-related diseases, including immune thrombocytopenic purpura, autoimmune neuropathies, systemic lupus erythematosus, Guillain-Barré syndrome, myasthenia gravis, Kawasaki disease, skin blistering diseases. The intravenous administration of exogenously pool...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 社论

    doi:

    authors: Luzi G,Bongiorno F,Paparo Barbaro S,Bruno G

    更新日期:2009-01-01 00:00:00

  • Comparison of the primary stabilities of conical and cylindrical endosseous dental implants: an in-vitro study.

    abstract::The aim of this study is to determine the differences in primary stability between conical and cylindrical dental implants. The insertion and removal torques were the parameters used to measure the primary stability of the implants. Ten conical and cylindrical dental implants were positioned in polyurethane foam block...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: Aleo E,Varvara G,Scarano A,Sinjari B,Murmura G

    更新日期:2012-01-01 00:00:00

  • Binding of nuclear factors to the IFN-gamma consensus sequence of the human HLA-DR alpha gene: effects of IFN-gamma on tumor cell lines.

    abstract::The binding of nuclear proteins from human tumor cells to synthetic double stranded oligonucleotides mimicking upstream regions of the HLA-DR alpha gene was studied. As the HLA-DR alpha gene is inducible by interferon(IFN)-gamma, nuclear extracts were also purified from IFN-gamma treated cells. Our data indicate that ...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 杂志文章

    doi:

    authors: Gambari R,Barbieri R,Nastruzzi C,Feriotto G,Piva R,Natali PG,Giacomini P

    更新日期:1990-07-01 00:00:00

  • Influence of titanium laser surface geometry on proliferation and on morphological features of human mandibular primary osteoblasts.

    abstract::The aim of this study is to assess in vitro the proliferation and the morphological changes of primary osteoblast-like cells (HOst) seeded on titanium dish grade 4 and 5 with different roughness and different titanium grade: machined (M), sandblasted (SBT), laser-treated with pitches of 20-microm diameter and 30-micro...

    journal_title:Journal of biological regulators and homeostatic agents

    pub_type: 临床试验,杂志文章

    doi:

    authors: Sinjari B,Guarnieri S,Diomede F,Merciaro I,Mariggio MA,Caputi S,Trubiani O

    更新日期:2012-07-01 00:00:00