Related Experiment Video

Updated: Jul 29, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms

A Bonni1, A Brunet, A E West

  • 1Division of Neuroscience, Children's Hospital, and Department of Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.

Science (New York, N.Y.)
|November 13, 1999
PubMed

Insights

The Ras-mitogen-activated protein kinase (MAPK) pathway promotes cell survival by inactivating the pro-apoptotic protein BAD and activating the transcription factor CREB. This dual mechanism enhances neuronal survival by blocking cell death and promoting pro-survival genes.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Neuroscience

Background:

  • The Ras-mitogen-activated protein kinase (MAPK) signaling pathway plays a crucial role in regulating cell survival.
  • Understanding the precise mechanisms by which MAPK signaling promotes cell survival is essential for developing therapeutic strategies against diseases involving aberrant cell death.

Purpose of the Study:

  • To elucidate the molecular mechanisms through which the Ras-MAPK signaling pathway mediates growth factor-dependent cell survival.
  • To investigate the roles of MAPK-activated kinases (Rsks) in the regulation of pro-apoptotic and pro-survival proteins.

Main Methods:

  • In vitro and in vivo biochemical assays to study protein phosphorylation.
  • Analysis of apoptosis induction and inhibition in neuronal cells.
  • Western blotting and reporter gene assays to assess protein modification and gene transcription.

Main Results:

  • MAPK-activated kinases (Rsks) were found to phosphorylate the pro-apoptotic protein BAD at serine 112, suppressing BAD-mediated apoptosis in neurons.
  • Rsks also phosphorylate the transcription factor CREB (cAMP response element-binding protein) at serine 133.
  • Phosphorylation of CREB at serine 133 promoted cell survival, while its inhibition triggered apoptosis.

Conclusions:

  • The MAPK signaling pathway promotes cell survival through a dual mechanism.
  • This involves the posttranslational modification and inactivation of the pro-apoptotic protein BAD.
  • It also involves the increased transcription of pro-survival genes mediated by CREB activation.

More Related Videos

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

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...