Related Experiment Video

Updated: Jul 14, 2026

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
08:38

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS

Published on: November 8, 2015

Phosphorylation of Bcl10 negatively regulates T-cell receptor-mediated NF-kappaB activation

Hu Zeng1, Lie Di, Guoping Fu

  • 1The Blood Research Institute, 8727 Watertown Plank Road, Milwaukee, WI 53226, USA.

Molecular and Cellular Biology
|May 16, 2007
PubMed

Insights

Phosphorylation of Bcl10 (B-cell lymphoma 10) at S138 by T-cell activation down-regulates its protein levels. This phosphorylation negatively regulates T-cell receptor-mediated NF-kappaB activation and enhances interleukin-2 production.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Bcl10 (B-cell lymphoma 10) is a crucial adaptor protein in NF-kappaB activation and lymphocyte functions.
  • Antigen receptor signaling pathways are critical for adaptive immunity and lymphocyte development.

Purpose of the Study:

  • To investigate the role of Bcl10 phosphorylation in T-cell activation.
  • To identify specific phosphorylation sites on Bcl10 induced by T-cell receptor (TCR) signaling.
  • To elucidate the functional consequences of Bcl10 phosphorylation on NF-kappaB activation and cytokine production.

Main Methods:

  • Utilized T-cell activation models to study Bcl10 phosphorylation patterns.
  • Employed site-directed mutagenesis to alter specific serine residues (e.g., S138) in Bcl10.
  • Assessed ubiquitination, degradation, NF-kappaB activation, and interleukin-2 production following T-cell stimulation.

Main Results:

  • T-cell activation induces monophosphorylation and biphosphorylation of Bcl10.
  • Serine 138 (S138) was identified as a key TCR-induced phosphorylation site on Bcl10.
  • Mutation of S138 to alanine impaired Bcl10 ubiquitination and degradation.
  • S138 phosphorylation negatively regulates Bcl10 protein levels, prolonging NF-kappaB activation and enhancing IL-2 production.

Conclusions:

  • Phosphorylation of Bcl10 at S138 acts as a negative feedback mechanism in TCR signaling.
  • S138 phosphorylation regulates Bcl10 stability, impacting NF-kappaB pathway duration.
  • This finding provides insights into the regulation of T-cell immune responses.

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
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...
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...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...