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Related Concept Videos

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...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

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 are of three kinds RI, RII, and RIII. The RI...
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...
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...
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:
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...

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Related Experiment Video

Updated: May 22, 2026

Isolation, Identification, and Purification of Murine Thymic Epithelial Cells
07:20

Isolation, Identification, and Purification of Murine Thymic Epithelial Cells

Published on: August 8, 2014

Deconstructing Ras signaling in the thymus.

Robert L Kortum1, Connie L Sommers, John M Pinski

  • 1Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Molecular and Cellular Biology
|May 16, 2012
PubMed
Summary
This summary is machine-generated.

This study reveals functional redundancy between Ras guanine exchange factors (RasGEFs) Sos1 and RasGRP1 during T cell development. Their combined action ensures proper T cell selection, preventing errors in central tolerance.

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • T cell development requires precise signaling through the pre-T cell receptor (pre-TCR) and T cell receptor (TCR).
  • Ras guanine exchange factors (RasGEFs) like Sos1 and RasGRP1 mediate signals from these receptors to the small G protein Ras.
  • Sos1 is implicated in the pre-TCR checkpoint, while RasGRP1 is essential for the TCR checkpoint.

Purpose of the Study:

  • To investigate the independent and combined roles of Sos1, Sos2, and RasGRP1 in thymocyte development.
  • To elucidate the mechanisms by which RasGEFs regulate T cell selection at distinct developmental checkpoints.

Main Methods:

  • Utilized mouse models to assess thymocyte development.
  • Examined the impact of deleting specific RasGEFs (Sos1, Sos2, RasGRP1) individually and in combination.

Main Results:

  • Sos1 is the dominant RasGEF at the pre-TCR checkpoint, but combined Sos1/RasGRP1 deletion is needed to fully block development.
  • RasGRP1 deletion blocks positive selection, while combined RasGRP1/Sos1 deletion is necessary to inhibit negative selection.
  • Demonstrated functional redundancy between Sos1 and RasGRP1, particularly during negative selection.

Conclusions:

  • Sos1 and RasGRP1 exhibit functional redundancy during thymocyte development, especially at the negative selection stage.
  • This redundancy may serve as a failsafe mechanism to ensure appropriate central tolerance.
  • Understanding RasGEF function is critical for comprehending T cell repertoire formation and preventing autoimmunity.