Phospho-MTOR (S2448) Recombinant Monoclonal Antibody

The Phospho-MTOR (S2448) Recombinant Monoclonal Antibody is produced through a rigorous process. Initially, the genes encoding the MTOR antibody are isolated from rabbits immunized with a synthetic peptide derived from the human MTOR protein phosphorylated at S2448. These antibody genes are then cloned into specialized expression vectors and introduced into mammalian suspension cells for antibody expression and secretion. Subsequently, the antibody is purified using affinity chromatography, isolating the Phospho-MTOR (S2448) Recombinant Monoclonal Antibody from the cell culture supernatant. The antibody's functionality is then validated through a series of assays including ELISA, Western Blot, Immunohistochemistry, and Immunofluorescence, confirming its ability to specifically recognize human MTOR protein phosphorylated at S2448.

Phosphorylation of MTOR at S2448 is a crucial regulatory event in cellular signaling. MTOR, a serine/threonine kinase, plays a central role in regulating cell growth, proliferation, and survival. Phosphorylation at S2448 activates MTOR, promoting protein synthesis, cell growth, and cell survival.

MTOR, a serine/threonine protein kinase, is a central regulator of cellular metabolism, growth, and survival. It responds to various signals, including hormones, growth factors, nutrients, energy levels, and stress. MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins, functioning within two structurally and functionally distinct signaling complexes: mTORC1 (mTOR complex 1) and mTORC2 (mTOR complex 2).

Activated mTORC1 upregulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes the phosphorylation of EIF4EBP1, releasing its inhibition of the elongation initiation factor 4E (eiF4E). Additionally, mTORC1 phosphorylates and activates RPS6KB1 and RPS6KB2, further promoting protein synthesis by modulating the activity of downstream targets such as ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4.

The mTORC1 signaling cascade also controls the MiT/TFE factors TFEB and TFE3. In the presence of nutrients, mTORC1 mediates the phosphorylation of TFEB and TFE3, promoting their cytosolic retention and inactivation. However, under starvation or lysosomal stress, inhibition of mTORC1 leads to dephosphorylation and nuclear translocation of TFEB and TFE3, activating their transcription factor activity.

mTORC1 stimulates the pyrimidine biosynthesis pathway, both acutely through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and through delayed regulation by transcriptional enhancement of the pentose phosphate pathway, which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later stage in synthesis. This function is dependent on the mTORC1 complex.

mTORC1 regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1, an RNA polymerase III repressor. In parallel to protein synthesis, mTORC1 also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis, mTORC1 may also regulate mitochondrial biogenesis by regulating PPARGC1A.

mTORC1 negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, mTORC1 phosphorylates ULK1 at 'Ser-758', disrupting its interaction with AMPK and preventing ULK1 activation. mTORC1 also prevents autophagy through phosphorylation of the autophagy inhibitor DAP, and by phosphorylating RUBCNL/Pacer under nutrient-rich conditions. Additionally, mTORC1 prevents autophagy by mediating the phosphorylation of AMBRA1, inhibiting its ability to mediate ubiquitination of ULK1 and its interaction with PPP2CA.

mTORC1 exerts a feedback control on upstream growth factor signaling, which includes phosphorylation and activation of GRB10, an INSR-dependent signaling suppressor. Among other potential targets, mTORC1 may phosphorylate CLIP1 and regulate microtubules.

As part of the mTORC2 complex, MTOR regulates other cellular processes, including survival and organization of the cytoskeleton. It plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton through phosphorylation of PRKCA, PXN, and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'.

mTORC2 regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms. It plays an important regulatory role in the circadian clock function, regulating the period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks. MTOR phosphorylates SQSTM1, promoting interaction between SQSTM1 and KEAP1, and subsequent inactivation of the BCR(KEAP1) complex.

1. Silencing of TRPC5 and inhibition of autophagy reverses adriamycin drug resistance in breast carcinoma via CaMKKbeta/AMPKalpha/mTOR pathway. PMID: 28600513
2. Studies indicate that understanding mTOR network circuitry will provide insight into its deregulation in diabetes, cancer, and cardiovascular disease, but modeling in silico to elucidate how insulin activates mTORC2 remains poorly defined. PMID: 22457328
3. L-type amino acid transporter 1 (LAT1) inhibitor, BCH reduces the phosphorylation of mechanistic target of rapamycin kinase (mTOR) in fibroblast-like synoviocytes from patients with rheumatoid arthritis. mTOR inhibitor, temsirolimus, neutralizes the stimulation of interleukin-17 on LAT1. PMID: 29198077
4. These results indicate that, under stressful conditions, maintained mTORC1 signaling in cancer cells promotes survival by suppressing endogenous DNA damage, and may control cell fate through the regulation of CHK1. PMID: 28484242
5. Results demonstrated that ASCT2 and pmTOR protein levels were significantly higher in epithelial ovarian cancer (EOC) tissues and predicting a poor prognosis. The expression levels of ASCT2 and pmTOR in EOC were positively correlated indicating a synergistic effect on the growth and development of early EOC. PMID: 30272366
6. DEPTOR interaction with mTOR represses its kinase activity and rewires the mTOR signaling pathway. [review] PMID: 29897294
7. both SphK1 overexpression and S1P addition increased mTOR phosphorylation as shown by ELISA, while S1PR2 inhibition had the inverse effect. These data suggest that CerS6 and SphK1 regulate mTOR signaling in breast cancer cell proliferation. Moreover, mTOR activity can be regulated by the balance between S1P and C16ceramide, which is generated by CerS6. PMID: 30226616
8. Study demonstrate that the miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2. The study provides reliable evidence supporting the use of miR-495 as a novel potential target in the chemotherapy of GC. PMID: 30147110
9. a functional convergence between the mTOR pathway and IFITM3 proteins at endolysosomal membranes. PMID: 30301809
10. data on TFEB nucleo-cytoplasmic shuttling suggest an unpredicted role of mTOR in nuclear export. PMID: 30120233
11. In this review, we assess the use of mTOR inhibitors to treat age-related pathologies, discuss possible molecular mechanisms of action where evidence is available, and consider strategies to minimize undesirable side effects. PMID: 30096787
12. The expression of CXCR4 and mTOR were found to be negatively correlated with remission. Kaplan-Meier analysis indicated a significant decrease in the rate of progression-free survival (PFS) and in that of overall survival (OS) in patients positive for CXCR4 and mTOR expression. PMID: 28952842
13. results demonstrated that SSd induces autophagy through the CaMKKbeta-AMPK-mTOR signalling pathway in Autosomal dominant polycystic kidney disease (ADPKD) cells, indicating that SSd might be a potential therapy for ADPKD and that SERCA might be a new target for ADPKD treatment. PMID: 29675630
14. findings indicated that shikonin inhibits proliferation and promotes apoptosis in human endometrioid endometrial cancer (EEC) cells by modulating the miR-106b/PTEN/AKT/mTOR signaling pathway, suggesting shikonin could act a potential therapeutic agent in the EEC treatment. PMID: 29449346
15. Mammalian target of rapamycin pathway promotes aerobic glycolysis in esophageal squamous cell carcinoma by upregulating pyruvate kinase M2 isoform PMID: 29916308
16. The p53 dependence of Plk2 loss and tumor suppressor function in relationship to mTOR signaling may have therapeutic implications. PMID: 29448085
17. Expression of miRNAs Targeting mTOR and S6K1 Genes of mTOR Signaling Pathway Including miR-96, miR-557, and miR-3182 in Triple-Negative Breast Cancer. PMID: 29862445
18. these findings uncover a novel mechanism by which PML loss may contribute to mTOR activation and cancer progression via dysregulation of basal DDIT4 gene expression. PMID: 28332630
19. High mTOR expression is associated with periodontitis. PMID: 30218719
20. This review intends to provide an outline of the principal biological and molecular functions of mTOR. PMID: 30110936
21. High mTOR expression is associated with Pancreatic Ductal Adenocarcinoma Metastasis. PMID: 29386088
22. High mTOR expression is associated with prostate cancer. PMID: 29566977
23. Studies indicate that dysregulation leads to a number of metabolic pathological conditions, including obesity and type 2 diabetes [Review]. PMID: 30011848
24. In ASS1-knockout cells, DEPTOR, an inhibitor of mTORC1 signal, was downregulated and mTORC1 signaling was more activated in response to arginine. PMID: 28358054
25. This review addresses the role of mTOR-dependent autophagy dysfunction in a variety of neuropsychiatric disorders, to focus mainly on psychiatric syndromes including schizophrenia and drug addiction. [review] PMID: 30061532
26. This article reviews the role of mTOR in cellular processes involved in cancer cachexia and highlights the studies supporting the contribution of mTOR in cancer cachexia. [review] PMID: 30061533
27. High mTOR expression is associated with aggressive pathology in urologic cancers. PMID: 29657089
28. miR-212 and mTOR signalings may form a positive regulation loop in maintaining cellular homeostasis. PMID: 30021100
29. High p-mTOR expression is associated with increased lymphangiogenesis and lymph node metastasis in prostate adenocarcinoma. PMID: 29544697
30. RIO kinase 3 (RIOK3) positively regulates the activity of the AKT/mTOR pathway in glioma cells. PMID: 29233656
31. Targeted profiling of RNA translation reveals mTOR-4EBP1/2-independent translation regulation of mRNAs encoding ribosomal proteins. PMID: 30224479
32. Results show that mTOR expression is regulated by PPP2R2D which influences its protein phosphorylation level contributing to gastric cancer progression. PMID: 29568966
33. We performed quantitative mass spectrometry of IAV1918-infected cells to measure host protein dysregulation. Selected proteins were validated by immunoblotting and phosphorylation levels of members of the PI3K/AKT/mTOR pathway were assessed. PMID: 29866590
34. Using an mTORspecific signalling pathway phospho array we revealed that NVPBEZ235 significantly decreased phosphorylation of 4EBP1 (Thr70), the downstream target of mTORC1. PMID: 29845289
35. The essential role of mTOR in the endocrine therapy resistance in estrogen receptor-positive, HER2-negative breast cancer.[review] PMID: 29086897
36. MiR-206 inhibits the development of epithelial ovarian cancer cell by directly targeting c-Met and inhibiting the c-Met/AKT/mTOR signaling pathway. PMID: 29807226
37. our findings identified LSD1 as a novel negative regulator of autophagy through the mTOR signaling pathway in ovarian cancer HO8910 cells and indicated that LSD1 may function as a driving factor of ovarian cancer progression via deregulating autophagy. PMID: 29749504
38. These results suggested that silibinin induced glioblastoma cell apoptosis concomitant with autophagy which might be due to simultaneous inhibition of mTOR and YAP and silibinin induced autophagy exerted a protective role against cell apoptosis in both A172 and SR cells. PMID: 29780826
39. BEX4 positively regulated the expression of OCT4, silencing of which reduced the proliferation of A549 and H1975cells with over-expressed BEX4. PMID: 29660335
40. Study demonstrates that high mTOR expression is associated with poor clinical outcome in acute lymphoblastic leukemia. PMID: 29076004
41. mTOR drives innate-like antibody responses by linking proximal transmembrane activator and CAML interactor signaling events with distal immunometabolic transcription programs. PMID: 29133782
42. piperine reduced the expression of pAkt, MMP9 and pmTOR. Together, these data indicated that piperine may serve as a promising novel therapeutic agent to better overcome prostate cancer metastasis. PMID: 29488612
43. Generation of 2-hydroxyglutarate by mutated IDH1/2 leads to the activation of mTOR by inhibiting KDM4A. PMID: 27624942
44. High mTOR expression is associated with gastric cancer. PMID: 29328491
45. The authors demonstrate that, particularly when autophagy is upregulated, varicella-zoster virus inhibits mTOR-mediated late-stage autophagic flux, likely at the point where autophagosomes and lysosomes fuse or where vesicle contents are degraded. Importantly, inhibition of autophagy yields higher varicella-zoster virus titers. PMID: 30053655
46. Identification of a functional mTOR targeted multigene signature robustly discriminates between normal prostate tissues, primary tumors, and hormone refractory metastatic samples but is also predictive of cancer recurrence PMID: 28724614
47. 2-ME reduced the production of CTGF and collagen I in SSc fibroblasts induced by hypoxia through PI3K/Akt/mTOR/HIF-1alpha signalling and inhibited the proliferation of fibroblasts. These findings suggested that 2-ME could be employed as a promising antifibrotic therapy for SSc PMID: 29905853
48. miR33a5p inhibited the proliferation of lung adenocarcinoma cells, enhanced the antitumor effect of celastrol, and improved sensitivity to celastrol by targeting mTOR in lung adenocarcinoma in vitro and in vivo PMID: 29484434
49. miR-181 may be a novel and important regulator of cisplatin-resistant non-small cell lung cancer by serving a role in the regulation of apoptosis, as an established rate-limiting miRNA target. PMID: 29484437
50. Evaluation of the potential mechanism demonstrated that TRIM28 promoted cervical cancer cell growth by activating the mammalian target of rapamycin (mTOR) signaling pathway. In support of this finding, TRIM28-induced cell proliferation was abolished by treatment with everolimus, a specific mTOR inhibitor PMID: 29393469

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HGNC: 3942

OMIM: 601231

KEGG: hsa:2475

STRING: 9606.ENSP00000354558

UniGene: Hs.338207