Related Experiment Video

Updated: Oct 7, 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

Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor

H K Lin1, S Yeh, H Y Kang

  • 1George Whipple Laboratory for Cancer Research, Department of Pathology, and The Cancer Center, University of Rochester, Rochester, NY 14642, USA.

Proceedings of the National Academy of Sciences of the United States of America
|June 19, 2001
PubMed

Insights

Akt serine-threonine kinase phosphorylates the androgen receptor (AR), impacting AR transactivation and androgen-mediated apoptosis. This reveals a molecular link between Akt signaling and AR pathways in cell survival.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • Akt serine-threonine kinase is known to promote cell survival through antiapoptotic effects.
  • The precise mechanisms by which Akt influences apoptosis, particularly in relation to the androgen receptor (AR), are not fully elucidated.
  • Understanding Akt's role in AR-mediated apoptosis is crucial for deciphering cell survival pathways.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying the interaction between Akt signaling and the androgen receptor (AR).
  • To determine if Akt directly phosphorylates the AR and how this affects AR function and apoptosis.
  • To elucidate the role of Akt in regulating AR target genes and androgen/AR-mediated apoptosis.

Main Methods:

  • Phosphorylation site mapping of the androgen receptor (AR) by Akt serine-threonine kinase.
  • Site-directed mutagenesis of identified phosphorylation sites (Ser-210 and Ser-790) on the AR.
  • Analysis of AR transactivation activity, AR target gene expression (e.g., p21), and apoptosis levels.
  • Investigation of the interaction between AR and AR coregulators.

Main Results:

  • Akt directly phosphorylates the androgen receptor (AR) at Ser-210 and Ser-790.
  • Mutation of AR Ser-210 reverses Akt-mediated suppression of AR transactivation.
  • Activation of the phosphatidylinositol-3-OH kinase/Akt pathway suppresses AR target genes like p21 and reduces androgen/AR-mediated apoptosis.
  • This reduction in apoptosis may involve inhibited interaction between AR and its coregulators.

Conclusions:

  • Akt serine-threonine kinase directly phosphorylates the androgen receptor (AR), modulating its activity.
  • This cross-talk between Akt and AR signaling pathways provides a molecular basis for Akt's role in promoting cell survival.
  • Findings enhance understanding of Akt's function in androgen/AR-mediated apoptosis and may have implications for cancer research.

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 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...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Abnormal Proliferation02:23

Abnormal 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...