Related Experiment Video

Updated: Jul 19, 2026

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

Regulation of androgen receptor activity by tyrosine phosphorylation

Zhiyong Guo1, Bojie Dai, Tianyun Jiang

  • 1Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.

Cancer Cell
|October 19, 2006
PubMed

Insights

Growth factors trigger tyrosine phosphorylation of the androgen receptor (AR), crucial for prostate cancer growth. Inhibiting this AR modification slows tumor growth, especially in hormone-refractory cases.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The androgen receptor (AR) plays a critical role in prostate cancer cell proliferation.
  • Hormone-refractory prostate cancer (HRPC) presents a significant clinical challenge.
  • Growth factor signaling pathways are often dysregulated in advanced cancers.

Purpose of the Study:

  • To investigate the role of tyrosine phosphorylation of the androgen receptor (AR) in prostate cancer.
  • To identify the kinases responsible for AR tyrosine phosphorylation.
  • To determine the impact of AR tyrosine phosphorylation on prostate cancer growth, particularly under androgen-depleted conditions.

Main Methods:

  • Analysis of AR tyrosine phosphorylation in prostate cancer cells and tumors.
  • Site-directed mutagenesis of the major tyrosine phosphorylation site on AR.
  • Assays to measure Src tyrosine kinase activity.
  • Correlation studies between AR tyrosine phosphorylation and Src activity in human prostate tumors.

Main Results:

  • Tyrosine phosphorylation of AR is induced by growth factors and elevated in hormone-refractory prostate tumors.
  • Mutation of the key tyrosine phosphorylation site significantly inhibited prostate cancer cell growth in androgen-depleted conditions.
  • Src tyrosine kinase was identified as a likely kinase responsible for AR phosphorylation.
  • A positive correlation was observed between AR tyrosine phosphorylation and Src tyrosine kinase activity in human prostate tumors.

Conclusions:

  • Growth factors and associated tyrosine kinases can induce AR tyrosine phosphorylation.
  • AR tyrosine phosphorylation, potentially mediated by Src kinase, may promote prostate cancer growth under androgen-depleted conditions.
  • Targeting AR tyrosine phosphorylation represents a potential therapeutic strategy for hormone-refractory prostate cancer.

More Related Videos

Development and Application of Rapamycin-regulated Tyrosine Phosphatases06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay09:07

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Published on: December 19, 2018

Related Concept Videos

Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/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...
mTOR Signaling and Cancer Progression03:03

mTOR 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...
mTOR Signaling and Cancer Progression03:03

mTOR 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...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include: