Related Experiment Video
Updated: Nov 22, 2025
15:05
Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
Published on: May 20, 2020
9.0K
Follicular Lymphoma-associated BTK Mutations are Inactivating Resulting in Augmented AKT Activation.
Nan Hu1, Fangyang Wang1, Tianyu Sun1
1Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, Michigan.
Summary
Novel Bruton tyrosine kinase (BTK) mutations in follicular lymphoma destabilize the protein and enhance AKT signaling, impacting targeted therapy development. These findings reveal unexpected properties of BTK mutations in lymphoma.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Recent discovery of Bruton tyrosine kinase (BTK) mutations in follicular lymphoma.
- BTK is a key regulator of B-cell receptor (BCR) signaling.
Purpose of the Study:
- Investigate the functional properties of novel somatic BTK mutations identified in follicular lymphoma.
- Determine the impact of these mutations on BCR-induced signal transduction pathways.
Main Methods:
- Identified BTK mutations in follicular lymphoma and transformed follicular lymphoma cases.
- Reconstituted wild-type (WT) and mutant BTK in engineered lymphoma cell lines.
- Measured BCR-induced signaling events in cell lines and primary human follicular lymphoma B cells.
Main Results:
- BTK mutants destabilized BTK protein; some were kinase-dead.
- BTK mutants induced exaggerated AKT phosphorylation in response to BCR crosslinking.
- Elevated AKT phosphorylation was observed in all follicular lymphoma B cells, irrespective of BTK mutation status.
Conclusions:
- Follicular lymphoma-associated BTK mutations exhibit novel, unexpected functional properties.
- These findings have direct implications for the development of targeted therapies for follicular lymphoma.
- Augmented AKT signaling in follicular lymphoma can be targeted by PI3Kδ inhibitors.
Related Concept Videos
01:22PI3K/mTOR/AKT Signaling Pathway
4.7K
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...
4.7K
03:03mTOR Signaling and Cancer Progression
4.1K
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...
The mTOR pathway or the...
4.1K
01:31The Intrinsic Apoptotic Pathway
7.5K
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...
7.5K
02:34Inhibition of Cdk Activity
5.3K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.3K
01:20The JAK-STAT Signaling Pathway
10.5K
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...
10.5K
02:57Targeted Cancer Therapies
8.1K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
8.1K