Related Experiment Video

Updated: Nov 6, 2025

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

6.3K

ERK phosphorylation is RAF independent in naïve and activated B cells but RAF dependent in plasma cell

Laura Scheffler1, Samantha Feicht1,2, Tea Babushku1

  • 1Research Unit of Gene Vectors, Helmholtz Center Munich, German Research Center for Environmental Health GmbH, Marchioninistrasse 25, D-81377 Munich, Germany.

Science Signaling
|May 12, 2021
PubMed

Insights

Raf-1 and B-Raf kinases are crucial for B cell selection and plasma cell differentiation. Their absence leads to increased ERK phosphorylation via RAF-independent pathways, impacting B cell development.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • The mitogen-activated protein kinase and extracellular signal-regulated kinase (MAPK-ERK) pathway regulates critical B cell differentiation processes.
  • RAF kinases (Raf-1 and B-Raf) are key intermediates in this pathway.

Purpose of the Study:

  • To investigate the roles of Raf-1 and B-Raf in B cell selection, differentiation, and ERK signaling.
  • To elucidate the mechanisms of ERK activation in the absence of RAF kinases.

Main Methods:

  • Analysis of mice with B cell-specific deletion of Raf1, Braf, or both.
  • Assessment of B cell populations, differentiation stages, and ERK phosphorylation levels.
  • Investigation of RAF-independent pathways, including phosphoinositide 3-kinase (PI3K).

Main Results:

  • Raf-1 and B-Raf cooperate in positive selection of pre-B and transitional B cells and in plasma cell differentiation initiation.
  • Genetic or chemical inactivation of RAFs resulted in increased ERK phosphorylation in mature B cells.
  • ERK activation in RAF-deficient B cells involved RAF-independent pathways, notably PI3K.
  • A marked increase in ERK phosphorylation during the activated B cell to pre-plasmablast transition was dependent on Raf-1 and B-Raf.

Conclusions:

  • Raf-1 and B-Raf are essential for the increase in ERK phosphorylation during the transition to plasma cell differentiation.
  • These RAF kinases are not required for ERK phosphorylation in naive or activated B cells.
  • The findings clarify the distinct roles of RAF kinases in B cell signaling and differentiation.

More Related Videos

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development09:32

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

Published on: June 15, 2017

8.9K
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

406

Related Concept Videos

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...
6.8K
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
14.6K
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...
6.6K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
4.6K
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...
6.8K
Cell Polarization by Rho Proteins01:21

Cell Polarization by Rho Proteins

Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
3.1K