Related Experiment Video

Updated: Jun 26, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

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

Published on: December 27, 2016

{beta}-Arrestin-2 Mediates Anti-apoptotic Signaling through Regulation of BAD Phosphorylation

Seungkirl Ahn1, Jihee Kim, Makoto R Hara

  • 1Departments of Medicine and Biochemistry and Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.

The Journal of Biological Chemistry
|January 28, 2009
PubMed

Insights

Beta-arrestin-2 acts as a signal transducer, mediating anti-apoptotic effects via the angiotensin ATII 1A receptor. This pathway involves ERK/p90RSK and PI3K/AKT signaling, ultimately protecting cells from apoptosis.

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Biochemistry

Background:

  • Beta-arrestins were initially identified as terminators of G protein-coupled receptor (GPCR) signaling.
  • Emerging evidence suggests beta-arrestins also function as signal transducers, but their physiological roles remain incompletely understood.

Purpose of the Study:

  • To investigate the role of beta-arrestin-2 in mediating cellular cytoprotective signaling.
  • To elucidate the specific signaling pathways involved in beta-arrestin-2-mediated anti-apoptotic effects.

Main Methods:

  • Utilized rat vascular smooth muscle cells and HEK-293 cells expressing the angiotensin ATII 1A receptor.
  • Investigated the activation of ERK/p90RSK and PI3K/AKT pathways.
  • Employed an angiotensin analog (SII) and beta-arrestin-2 small interfering RNA (siRNA) for functional studies.

Main Results:

  • Beta-arrestin-2 mediates anti-apoptotic signaling stimulated by the angiotensin ATII 1A receptor.
  • Receptor stimulation activates ERK/p90RSK and PI3K/AKT pathways, leading to BAD phosphorylation and inactivation.
  • An angiotensin analog (SII) that activates beta-arrestin but not G protein signaling also stimulates these anti-apoptotic effects.

Conclusions:

  • Beta-arrestin-2 plays a crucial role in mediating cytoprotective functions of 7-transmembrane receptors.
  • Defines the specific biochemical pathways (ERK/p90RSK, PI3K/AKT) through which beta-arrestin-2 exerts its anti-apoptotic effects.

More Related Videos

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

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...
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...
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...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.