Related Experiment Video

Updated: Aug 11, 2026

Generation of Human Chimeric Antigen Receptor Regulatory T Cells
10:29

Generation of Human Chimeric Antigen Receptor Regulatory T Cells

Published on: January 3, 2025

Nore1B regulates TCR signaling via Ras and Carma1

Kazuhiro Ishiguro1, Joe Avruch, Aimee Landry

  • 1Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.

Cellular Signalling
|March 8, 2006
PubMed

Insights

Nore1B protein is crucial for immune cell communication by recruiting active Ras to the interface between cells. This interaction is vital for T cell receptor signaling and Ras-mediated activation of downstream pathways.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Signaling

Background:

  • Nore1A and Nore1B are isoforms of a protein family, with Nore1B being key in immune signaling.
  • Both isoforms possess a Ras/Rap association (RA) domain, but Nore1A has additional binding motifs.
  • The interaction between Nore1B, Carma1, and Ras is critical for T cell activation.

Purpose of the Study:

  • To investigate the role of Nore1B in immune cell signaling pathways.
  • To elucidate the interaction between Nore1B, Carma1, and active Ras.
  • To determine Nore1B's function in T cell receptor (TCR) mediated NF-kappaB activation and Ras-ERK signaling.

Main Methods:

  • Utilized RNA interference to knock down Nore1B expression.
  • Analyzed NF-kappaB activation in response to TCR ligation, TNFalpha, and lipoteichoic acid.
  • Assessed KiRas GV12-mediated ERK1 activation and Elk1 reporter activity.
  • Examined the polarized redistribution of Ras at the immune cell interface.

Main Results:

  • Carma1 binds to Nore1A and Nore1B via the RA domain and interacts with active Ras in the presence of Nore1B.
  • Nore1B knockdown attenuated TCR-induced NF-kappaB activation but not TNFalpha or lipoteichoic acid-induced activation.
  • Nore1B is essential for KiRas GV12-mediated ERK1 activation and Elk1 reporter activity.
  • Knockdown of Nore1B impaired the polarized redistribution of Ras at the B cell-T cell interface.

Conclusions:

  • Endogenous Nore1B recruits active Ras to the T cell interface.
  • Nore1B mediates the interaction between Ras and Carma1, playing a critical role in TCR signaling.
  • Nore1B is indispensable for Ras-mediated activation of downstream signaling pathways in T cells.

More Related Videos

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation09:04

Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation

Published on: September 7, 2010

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...
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:
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...