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Related Concept Videos

mTOR Signaling and Cancer Progression03:03

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The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
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The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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Signal integration in the (m)TORC1 growth pathway.

Kailash Ramlaul1, Christopher H S Aylett1

  • 1Section of Structural Biology, Department of Medicine, Imperial College London, SW7 2AZ, UK.

Frontiers in Biology
|September 14, 2020
PubMed
Summary

The Target Of Rapamycin (TOR) pathway regulates cell growth by integrating diverse signals. Understanding its upstream components is crucial for developing therapies for diseases like cancer and diabetes.

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GATOR complexRag GTPasesRhebTSC complexmTORC1nutrient sensing

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Signaling

Background:

  • The Target Of Rapamycin (TOR) pathway is central to eukaryotic cell growth regulation.
  • TOR forms distinct complexes (TORC1 and TORC2) that control biosynthesis and autophagy in response to nutrients, growth factors, and stress.
  • Dysregulation of mTORC1 signaling is implicated in various pathologies, including cancer, neurological disorders, and metabolic diseases like diabetes.

Purpose of the Study:

  • To analyze molecular and structural studies on the upstream components of the mTORC1 signaling pathway.
  • To elucidate the mechanisms of mTORC1 repression, activation, and signal integration.
  • To bridge the gap in understanding how diverse cellular signals are integrated to regulate cell growth.

Main Methods:

  • Comprehensive review and analysis of existing molecular and structural studies on mTORC1.
  • Detailed examination of upstream signaling components influencing mTORC1 activity.
  • Integration of findings from various studies to provide a cohesive overview.

Main Results:

  • Recent structural studies offer mechanistic insights into mTORC1 activation.
  • The precise integration of upstream cellular signals remains incompletely understood.
  • Significant progress has been made in understanding mTORC1 repression and activation.

Conclusions:

  • A molecular understanding of mTORC1 signal integration is essential for comprehending cell growth regulation.
  • Further research is needed to establish a mechanistic understanding of the upstream pathways controlling mTORC1.
  • This knowledge is critical for developing therapeutic strategies targeting mTORC1 in various diseases.