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Related Concept Videos

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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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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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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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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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Understanding MAPK Signaling Pathways in Apoptosis.

Jicheng Yue1, José M López2

  • 1School of Biology and Basic Medical Sciences, Soochow University Medical College, 199 Ren'ai Road, Suzhou 215123, China.

International Journal of Molecular Sciences
|April 2, 2020
PubMed
Summary

Mitogen-activated protein kinase (MAPK) pathways have dual roles in apoptosis, acting as activators or inhibitors. Understanding MAPK signaling properties and feedback loops helps predict cellular decisions during apoptosis.

Keywords:
ERKJNKMAPKapoptosiscaspasesfeedback loopsoocytesp38protein kinasessignaling

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Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitogen-activated protein kinase (MAPK) signaling pathways are crucial regulators of diverse biological processes.
  • MAPKs exhibit a dual role in apoptosis, functioning as either activators or inhibitors based on cellular context and stimuli.

Purpose of the Study:

  • To review pro- and anti-apoptotic mechanisms regulated by MAPKs.
  • To elucidate the crosstalk between different MAPK pathways.
  • To describe MAPK signaling properties and their role in apoptosis.

Main Methods:

  • Literature review of MAPK signaling in apoptosis.
  • Analysis of MAPK signaling properties like ultrasensitivity and hysteresis.
  • Examination of positive feedback loops in apoptotic pathways.
  • Case study using Xenopus oocytes to investigate osmostress-induced apoptosis.

Main Results:

  • MAPKs play complex, context-dependent roles in apoptosis.
  • Positive feedback loops are prevalent in apoptosis, contributing to irreversible cellular decisions.
  • MAPK behavior can be predicted based on stimulus characteristics.

Conclusions:

  • MAPK signaling pathways are key drivers of apoptosis.
  • Understanding MAPK dynamics, including feedback mechanisms, is essential for comprehending irreversible cellular fate decisions.
  • The study provides insights into MAPK involvement in osmostress-induced apoptosis.