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MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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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.
Convergence and divergence, and cross-talk between signaling pathways
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cAMP-dependent Protein Kinase Pathways01:25

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Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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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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The Unfolded Protein Response01:37

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The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
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MAPK-ERK Pathway.

Jong-In Park1

  • 1Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

International Journal of Molecular Sciences
|June 10, 2023
PubMed
Summary
This summary is machine-generated.

Extracellular signal-regulated kinase (ERK) is a key cell cycle regulator identified in mammalian cells. This protein kinase plays a crucial role in cellular processes and signaling pathways.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • The extracellular signal-regulated kinase (ERK) pathway is a critical signaling cascade involved in various cellular functions.
  • ERK, a Ser/Thr protein kinase, was initially identified for its role in regulating the cell cycle in mammalian cells.

Discussion:

  • The discovery of ERK marked a significant advancement in understanding cell cycle regulation.
  • Further research has elucidated ERK's involvement in diverse biological processes beyond the cell cycle.

Key Insights:

  • ERK is a fundamental component of intracellular signaling networks.
  • Its initial characterization highlighted its importance in controlling cell proliferation and differentiation.

Outlook:

  • Continued investigation into the ERK pathway promises new insights into disease mechanisms.
  • Targeting ERK signaling holds potential for therapeutic interventions in cancer and other diseases.