Related Experiment Video

Updated: May 30, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Perspectives on the role of mTORC2 in B lymphocyte development, immunity and tumorigenesis

Adam S Lazorchak1, Bing Su

  • 1Department of Immunobiology and the Vascular Biology and Therapeutic Program, Yale School of Medicine, New Haven, CT 06519, USA.

Protein & Cell
|August 9, 2011
PubMed

Insights

Mammalian target of rapamycin complex 2 (mTORC2) regulates B cell survival and immunoglobulin gene recombination. mTORC2 inhibition may increase cancer risk by impairing this process in dividing B cells.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Mammalian target of rapamycin complex 2 (mTORC2) is a critical mediator of phosphoinositol-3-kinase (PI3K) signaling pathways.
  • mTORC2 plays a significant role in lymphocyte development, homeostasis, and immune responses.
  • The precise functions and regulatory mechanisms of mTORC2 in B and T cells require further elucidation.

Purpose of the Study:

  • To investigate the role of mTORC2 in B cell function, specifically survival and immunoglobulin (Ig) gene recombination.
  • To explore the molecular mechanisms underlying mTORC2's regulation of these processes in B cells.
  • To assess the implications of mTORC2 signaling for B cell-related pathologies and cancer development.

Main Methods:

  • Utilized genetic and pharmacologic approaches to modulate mTORC2 activity.
  • Analyzed B cell survival and immunoglobulin gene recombination in bone marrow B cells.
  • Investigated the involvement of Akt2 and FoxO1 in mTORC2-mediated signaling pathways.
  • Examined the effect of mTORC2 on Akt protein stability.

Main Results:

  • mTORC2 is crucial for regulating the survival of bone marrow B cells.
  • mTORC2 controls immunoglobulin gene recombination in B cells via an Akt2-FoxO1 dependent pathway.
  • Ig recombination is suppressed in proliferating B cells to prevent DNA damage.
  • mTORC2 regulates Akt protein stability, suggesting a novel therapeutic target.

Conclusions:

  • mTORC2 signaling is essential for maintaining B cell homeostasis and preventing aberrant immunoglobulin gene recombination.
  • Inhibition of mTORC2 may lead to increased B cell tumor development due to impaired suppression of Ig recombination in dividing cells.
  • Targeting mTORC2's regulation of Akt protein stability presents a potential new strategy for cancer treatment.

More Related Videos

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation09:37

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

Published on: March 15, 2018

Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines06:00

Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines

Published on: September 13, 2017

Related Concept Videos

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...
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...
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...
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...
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...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...