Related Experiment Video
Updated: Jul 14, 2026
11:44
A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
Pin1 is required for the Ser727 phosphorylation-dependent Stat3 activity
1Signal Transduction Laboratory, Institute of Molecular and Cell Biology, Singapore, Republic of Singapore.
Oncogene
|June 15, 2007
Summary
Peptidyl-prolyl cis/trans isomerase 1 (Pin1) enhances Signal transducer and activator of transcription 3 (Stat3) activity by interacting with its Ser727 phosphorylation site. This interaction promotes Stat3-driven gene expression and epithelial-mesenchymal transition in cancer cells.
Area of Science:
- Molecular Biology
- Cell Signaling
- Cancer Research
Background:
- Signal transducer and activator of transcription 3 (Stat3) is a key transcription factor in cytokine signaling.
- Constitutive Stat3 activation is implicated in various cancers, functioning as an oncogene.
- Stat3 transcriptional activity is regulated by Tyr-phosphorylation, but the role of Ser727 phosphorylation remains unclear.
Purpose of the Study:
- To elucidate the mechanism by which Ser727 phosphorylation regulates Stat3 transcriptional activity.
- To investigate the role of peptidyl-prolyl cis/trans isomerase 1 (Pin1) in Stat3 regulation.
- To determine Pin1's impact on Stat3-mediated gene expression and cancer cell behavior.
Main Methods:
- Co-immunoprecipitation to assess Pin1-Stat3 interaction.
- Overexpression and knockdown studies of Pin1 in cancer cell lines.
- Reporter assays to measure Stat3 transcriptional activity.
- Western blotting to detect protein phosphorylation and expression.
- Analysis of epithelial-mesenchymal transition markers.
Main Results:
- Pin1 interacts with Stat3 upon cytokine/growth factor stimulation, specifically dependent on Ser727 phosphorylation.
- Pin1 overexpression enhances Stat3 transcriptional activity, target gene expression, and p300 coactivator recruitment.
- Pin1 deficiency compromises Stat3 activity and its downstream effects.
- Pin1 promotes Stat3-mediated epithelial-mesenchymal transition in breast cancer cells.
Conclusions:
- Pin1 acts as a novel regulator of Stat3 transcriptional activity through a Ser727 phosphorylation-dependent mechanism.
- Pin1 enhances Stat3 function by promoting its interaction with coactivators like p300.
- Pin1's role in Stat3-mediated EMT highlights its potential as a therapeutic target in Stat3-driven cancers.
Related Concept Videos
01:20The 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...
01:22PI3K/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...
01:22Amplifying 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...
01:11IP3/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...
01:42Phosphoinositides and PIPs
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
01:25cAMP-dependent Protein Kinase Pathways
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...