Related Experiment Video

Updated: Aug 8, 2026

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

Tyrphostins inhibit the epidermal growth factor receptor-mediated breakdown of phosphoinositides

I Posner1, A Gazit, C Gilon

  • 1Department of Biological Chemistry, Hebrew University of Jerusalem, Israel.

FEBS Letters
|November 6, 1989
PubMed

Insights

Epidermal growth factor (EGF) stimulates phosphatidylinositide production in cancer cells. Tyrphostins, EGF receptor kinase inhibitors, block this response, suggesting phospholipase C activation via EGF receptor phosphorylation.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Cancer Research

Background:

  • Epidermal growth factor (EGF) plays a crucial role in cell proliferation and signaling.
  • Phosphatidylinositides are key components of cell membranes involved in signal transduction.
  • A431 human epidermoid carcinoma cells and their EGF-dependent variants are used to study EGF signaling pathways.

Purpose of the Study:

  • To investigate the effect of EGF and the calcium ionophore A23187 on total phosphatidylinositide (IPT) levels in A431 cells.
  • To determine the role of EGF receptor kinase activity in the regulation of IPT production.
  • To elucidate the mechanism of phospholipase C activation in response to EGF.

Main Methods:

  • Treatment of A431 and A431/Clone 15-2 cells with EGF and A23187.
  • Quantification of total phosphatidylinositide (IPT) levels.
  • Inhibition studies using tyrphostins, potent EGF-receptor kinase inhibitors.

Main Results:

  • EGF and A23187 significantly increased IPT levels in both cell lines, with a more pronounced effect in EGF-dependent cells.
  • Tyrphostins inhibited both EGF- and ionophore-induced IPT increases, but more effectively inhibited the EGF-induced response.
  • The potency of tyrphostins in inhibiting IPT formation correlated with their potency as EGF-receptor kinase inhibitors.

Conclusions:

  • Phospholipase C activation is mediated by phosphorylation through the EGF receptor.
  • EGF signaling pathway is critical for regulating phosphoinositide metabolism in these cancer cells.
  • Tyrphostins demonstrate potential as inhibitors of EGF-driven signaling pathways.

More Related Videos

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes08:49

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes

Published on: March 14, 2021

Development and Application of Rapamycin-regulated Tyrosine Phosphatases06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

Related Concept Videos

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...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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...
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...
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...
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: