Related Experiment Video
Updated: Jul 19, 2025
10:31
The Drosophila Imaginal Disc Tumor Model: Visualization and Quantification of Gene Expression and Tumor Invasiveness Using Genetic Mosaics
Published on: October 6, 2016
11.2K
Cutting Edge: Induced Loss of Rasgrp1 in Peripheral CD4+ T Cells of Conditional Rasgrp1-Deficient Mice Reveals an
Yating Chang1, Praveen Manivannan1, Abbas Doosti1
1Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI.
Journal of Immunology (Baltimore, Md. : 1950)
|August 11, 2023
Summary
Ras guanine nucleotide-releasing protein 1 (RasGRP1) is crucial for activating Ras-ERK signaling in peripheral CD4+ T cells. Its absence blocks IL-2 synthesis and proliferation following T cell receptor stimulation.
Area of Science:
- Immunology
- Cell Signaling
- Molecular Biology
Background:
- Ras guanine nucleotide-releasing protein 1 (RasGRP1) is a guanine nucleotide exchange factor vital for T cell development and Ras-ERK pathway activation.
- Its precise role in mature peripheral T cells remains unclear due to abnormal phenotypes in constitutive knockout models.
Purpose of the Study:
- To investigate the function of RasGRP1 in mature peripheral CD4+ T cells using an inducible knockout model.
- To elucidate the role of RasGRP1 in T cell receptor/CD28-mediated signaling and activation.
Main Methods:
- Generated an inducible RasGRP1-deficient mouse model for acute gene disruption in peripheral CD4+ T cells.
- Analyzed TCR/CD28-mediated activation of the Ras-ERK signaling pathway.
- Assessed IL-2 synthesis, IL-2 receptor expression, and T cell proliferation.
Main Results:
- Acute deficiency of RasGRP1 blocked TCR/CD28-induced Ras-ERK signaling in peripheral CD4+ T cells.
- RasGRP1-deficient CD4+ T cells exhibited impaired IL-2 synthesis and high-affinity IL-2 receptor expression.
- Proliferation of RasGRP1-deficient CD4+ T cells in response to TCR/CD28 stimulation was significantly reduced.
Conclusions:
- RasGRP1 plays an essential role in TCR/CD28-induced Ras-ERK activation in mature peripheral CD4+ T cells.
- RasGRP1 is critical for the proper activation, IL-2 production, and proliferation of peripheral CD4+ T cells.
Related Concept Videos
01:07MAPK Signaling Cascades
5.7K
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...
5.7K
02:38The Ras Gene
6.3K
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...
Ras is a...
6.3K
01:24Small GTPases - Ras and Rho
4.0K
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:
Three regulatory proteins control their activity:
4.0K
01:20The JAK-STAT Signaling Pathway
9.0K
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...
9.0K
01:16TGF - β Signaling Pathway
7.4K
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...
7.4K
01:22T Cell Activation and Clonal Selection
808
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
808