Related Experiment Video

Updated: Aug 28, 2026

A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry
04:32

A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry

Published on: June 5, 2019

Distinct mechanisms of activation of Stat1 and Stat3 by platelet-derived growth factor receptor in a cell-free system

M L Vignais1, M Gilman

  • 1Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.

Molecular and Cellular Biology
|April 17, 1999
PubMed

Insights

Platelet-derived growth factor receptor (PDGFR) activates Stat1 directly, but Stat3 requires Janus kinases (JAKs) in a cell-free system. This reveals distinct biochemical mechanisms for STAT protein activation by PDGFR.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Signal transduction

Background:

  • Platelet-derived growth factor receptor (PDGFR) activation triggers downstream signaling cascades.
  • Janus kinases (JAKs) and Signal Transducers and Activators of Transcription (STATs) are key components in cellular communication.

Purpose of the Study:

  • To elucidate the distinct biochemical mechanisms underlying Stat1 and Stat3 activation by PDGFR.
  • To investigate the role of JAK proteins in PDGFR-mediated STAT activation.

Main Methods:

  • Development of a cell-free system using a membrane fraction overexpressing PDGFR.
  • Utilizing crude cytosol and purified recombinant STAT proteins for activation assays.
  • Employing antibodies against JAK proteins to deplete specific activities from the cytosol.

Main Results:

  • PDGFR-mediated activation of both Stat1 and Stat3 was observed in the cell-free system, dependent on PDGF and ATP.
  • Stat1 activation by PDGFR occurred independently of cytosolic or membrane factors.
  • Stat3 activation demonstrated a significant requirement for cytosolic factors, specifically JAK proteins.

Conclusions:

  • Stat1 activation by PDGFR involves a direct interaction with the receptor.
  • Stat3 activation by PDGFR is an indirect process requiring the involvement of JAK proteins.
  • Distinct molecular mechanisms govern the activation of Stat1 and Stat3 by PDGFR.

More Related Videos

Time-resolved Förster Resonance Energy Transfer Assays for Measurement of Endogenous Phosphorylated STAT Proteins in Human Cells07:12

Time-resolved Förster Resonance Energy Transfer Assays for Measurement of Endogenous Phosphorylated STAT Proteins in Human Cells

Published on: September 9, 2021

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Related Concept Videos

Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
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...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
IP3/DAG Signaling Pathway01:11

IP3/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...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...