Related Experiment Video

Updated: Jul 16, 2026

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

Identification of STAT3 as a specific substrate of breast tumor kinase

L Liu1, Y Gao, H Qiu

  • 1Department of Microbiology and Molecular Genetics, Stony Brook University, Stony Brook, NY 11794-8691, USA.

Oncogene
|March 29, 2006
PubMed

Insights

Breast tumor kinase (Brk) activates signal transducer and activator of transcription 3 (STAT3), promoting breast cancer cell proliferation. Suppressor of cytokine signaling 3 (SOCS3) was identified as a negative regulator of Brk activity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Breast tumor kinase (Brk) is a non-receptor tyrosine kinase found in over 60% of breast tumors.
  • The precise biological function and substrates of Brk in tumorigenesis are not well understood.

Purpose of the Study:

  • To identify physiological targets of Brk and elucidate its role in breast cancer.
  • To investigate the regulatory mechanisms of Brk activity.

Main Methods:

  • Investigated the interaction between Brk and signal transducer and activator of transcription 3 (STAT3) using biochemical assays.
  • Assessed STAT3 phosphorylation and transcriptional activity in cells expressing Brk.
  • Examined the effect of Brk and STAT3 co-expression on cellular proliferation.
  • Identified and characterized the interaction between Brk and suppressor of cytokine signaling 3 (SOCS3).

Main Results:

  • STAT3 was identified as a direct physiological substrate of Brk.
  • Brk expression led to tyrosine phosphorylation and transcriptional activation of STAT3.
  • STAT3 activation by Brk was specific, as other STAT family members were unaffected.
  • Co-expression of STAT3 and Brk enhanced cellular proliferation.
  • SOCS3 was identified as a novel negative regulator of Brk, capable of repressing its kinase activity.

Conclusions:

  • Brk directly targets and activates STAT3, contributing to oncogenesis in breast cancer.
  • Brk-mediated STAT3 activation promotes tumor cell proliferation.
  • SOCS3 negatively regulates Brk, suggesting a potential therapeutic target for controlling Brk signaling in breast cancer.

More Related Videos

Differentiation of Mouse Breast Epithelial HC11 and EpH4 Cells09:32

Differentiation of Mouse Breast Epithelial HC11 and EpH4 Cells

Published on: February 27, 2020

Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies09:01

Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies

Published on: July 3, 2025

Related Concept Videos

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...
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...
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...
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...