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Related Experiment Video

Updated: Feb 20, 2026

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method

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Published on: October 23, 2018

A lipid off-switch for mTORC1.

Alexander Wallroth¹, Volker Haucke¹

¹Department of Molecular Pharmacology & Cell Biology, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Straße 10, Berlin, Germany.

Molecular & Cellular Oncology

|October 24, 2017

Summary

Class II PI3Kβ (PI3KC2β) synthesizes phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] at endosomes, repressing mTORC1. This finding reveals PI3KC2β as a potential therapeutic target for cancer and diabetes.

Keywords:

cancer class II PI 3-kinase diabetes late endosomes/ lysosomes mTORC1 nutrient signaling phosphoinositides

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

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Published on: March 15, 2018

Area of Science:

Cellular metabolism and signaling
Molecular biology
Endosomal trafficking

Background:

Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cellular processes.
mTORC1 activity is implicated in metabolic diseases and cancer.
Phosphoinositide signaling pathways play critical roles in cell growth and survival.

Purpose of the Study:

To investigate the role of class II PI3Kβ (PI3KC2β) in regulating mTORC1.
To determine the localization and function of PI(3,4)P2 synthesis in mTORC1 signaling.
To identify PI3KC2β as a potential therapeutic target.

Main Methods:

Cellular assays to measure mTORC1 activity.
Biochemical analysis of phosphoinositide synthesis.
Localization studies using fluorescent microscopy.
Pharmacological inhibition of PI3KC2β.

Main Results:

PI3KC2β localizes to late endosomes/lysosomes.
PI3KC2β-mediated synthesis of phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] at these organelles represses mTORC1.
Inhibition of PI3KC2β activates mTORC1.

Conclusions:

Local PI(3,4)P2 synthesis by PI3KC2β is a novel mechanism for mTORC1 repression.
PI3KC2β is a critical regulator of mTORC1 signaling.
Targeting PI3KC2β offers a potential therapeutic strategy for diseases driven by aberrant mTORC1 activity, including cancer and diabetes.