Related Experiment Video

Updated: Aug 6, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

Suppression of IP3-mediated calcium release and apoptosis by Bcl-2 involves the participation of protein phosphatase

Liping Xu1, Dejuan Kong, Liping Zhu

  • 1Department of Pathology, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA.

Molecular and Cellular Biochemistry
|July 29, 2006
PubMed

Insights

Bcl-2 protein suppresses inositol trisphosphate (IP3)-sensitive calcium release by interacting with protein phosphatase 1 (PP1), thereby protecting cells from death. This mechanism involves regulating the IP3 receptor signaling complex.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The interplay between inositol trisphosphate (IP3) receptors and Bcl-2 in calcium (Ca2+) signaling remains unclear.
  • Bcl-2 is known for its role in cell death regulation, but its direct impact on Ca2+ signaling pathways is not fully elucidated.

Purpose of the Study:

  • To investigate the mechanism by which Bcl-2 suppresses IP3-sensitive Ca2+ release in MCF-7 cells.
  • To explore the potential role of protein phosphatase 1 (PP1) in mediating Bcl-2's effect on Ca2+ signaling.

Main Methods:

  • Utilized MCF-7 cells for experimental studies.
  • Employed phosphatase inhibition and RNA interference (RNAi) techniques.
  • Investigated protein-protein interactions within the IP3 receptor signaling complex.

Main Results:

  • Bcl-2 influences protein-protein interactions, potentially altering the balance between phosphatase (PP1) and kinase (PKA) activities on the IP3 receptor type 1 (IP3R1) signaling complex.
  • Bcl-2 competes with IP3R1 for binding to PP1.
  • This competition reduces IP3-mediated calcium signals.

Conclusions:

  • Bcl-2 suppresses IP3-mediated calcium release by inhibiting PP1 interaction with IP3R1.
  • This action protects cells from mitochondrial dysfunction and subsequent cell death.
  • The findings reveal a novel mechanism linking Bcl-2, calcium signaling, and cell survival.

More Related Videos

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity04:20

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity

Published on: February 9, 2024

Related Concept Videos

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...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
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 Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...