Related Experiment Video
Updated: May 10, 2026
08:45
Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
Published on: July 17, 2020
Pim2 is required for maintaining multiple myeloma cell growth through modulating TSC2 phosphorylation
Jing Lu1, Tatiana Zavorotinskaya, Yumin Dai
1Novartis Institutes for Biomedical Research, Emeryville, CA 94508, USA.
Blood
|July 3, 2013
Summary
Pim2 kinase is highly expressed in multiple myeloma (MM) cells and drives their proliferation. Inhibiting Pim2 kinase or its novel target TSC2 significantly halts MM cell growth by impacting mTOR-C1 signaling.
Area of Science:
- Hematologic Oncology
- Molecular Biology
- Cell Signaling
Background:
- Multiple myeloma (MM) is a prevalent hematologic malignancy with limited curative options.
- Recent therapeutic advancements have improved MM outcomes but have not led to a cure.
Purpose of the Study:
- To investigate the role of Pim2 kinase in multiple myeloma cell proliferation.
- To identify novel therapeutic targets and pathways involved in MM pathogenesis.
Main Methods:
- Utilized short hairpin RNAs (shRNAs) and a small-molecule inhibitor to interfere with Pim2 kinase activity.
- Assessed the impact of Pim2 inhibition on MM cell proliferation and mammalian target of rapamycin C1 (mTOR-C1) signaling.
- Identified and characterized TSC2 as a novel substrate of Pim2 kinase.
Main Results:
- Pim2 kinase expression is significantly elevated in MM cells.
- Functional inhibition of Pim2 kinase markedly reduces MM cell proliferation.
- Pim2 inhibition leads to decreased mTOR-C1 activity.
- Pim2 directly phosphorylates TSC2 at Ser-1798, alleviating TSC2-mediated suppression of mTOR-C1.
Conclusions:
- Pim2 kinase is essential for MM cell proliferation and represents a promising therapeutic target.
- A novel signaling pathway, Pim2-TSC2-mTOR-C1, is identified as a key driver of MM proliferation.
Related Concept Videos
02:23Abnormal 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...
03:03mTOR 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...
The mTOR pathway or the...
01:22PI3K/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...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:16TGF - 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...
02:34Inhibition of Cdk Activity
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...