Related Experiment Video

Updated: May 4, 2026

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

13.9K

PIP₃ induces the recycling of receptor tyrosine kinases

Vibor Laketa1, Sirus Zarbakhsh, Alexis Traynor-Kaplan

  • 11Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117 Heidelberg, Germany.

Science Signaling
|January 16, 2014
PubMed

Insights

Increased phosphatidylinositol 3,4,5-trisphosphate (PIP3) levels trigger epidermal growth factor receptor (EGFR) endocytosis and recycling. Polarity proteins like PARD3 are crucial for this PIP3-mediated receptor tyrosine kinase trafficking.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Receptor tyrosine kinases (RTKs), like epidermal growth factor receptor (EGFR), are downregulated via endocytosis, leading to degradation or recycling.
  • Understanding the precise mechanisms regulating RTK trafficking is crucial for comprehending cellular signaling and responsiveness.

Purpose of the Study:

  • To investigate the role of phosphatidylinositol 3,4,5-trisphosphate (PIP3) in regulating EGFR endocytosis and trafficking.
  • To identify key proteins involved in PIP3-mediated RTK recycling.

Main Methods:

  • Utilized clathrin- and dynamin-mediated endocytosis assays.
  • Performed RNA interference (RNAi) screening targeting lipid-binding domain proteins.
  • Analyzed receptor ubiquitination and phosphorylation levels.

Main Results:

  • Elevated PIP3 levels induced clathrin- and dynamin-dependent endocytosis of EGFR, distinct from transferrin or G protein-coupled receptors.
  • PIP3-induced internalization reduced EGFR ubiquitination and phosphorylation, promoting receptor recycling.
  • RNAi screen identified polarity complex proteins, including PARD3, as essential for PIP3-induced RTK recycling.

Conclusions:

  • PIP3 acts as a key regulator of RTK trafficking, influencing both endocytosis and subsequent recycling.
  • Polarity complex proteins, such as PARD3, play a critical role in PIP3-mediated RTK trafficking.
  • This regulatory pathway may enhance cellular sensitivity and responsiveness to growth factors.

More Related Videos

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development09:32

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

Published on: June 15, 2017

8.0K
Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells09:15

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells

Published on: October 20, 2022

2.4K

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...
15.5K
Phosphoinositides and PIPs01:42

Phosphoinositides 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...
7.7K
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...
15.3K
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:
4.4K
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...
12.5K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.0K