Related Experiment Video

Updated: Aug 13, 2026

Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

PI3K is required for insulin-stimulated but not EGF-stimulated ERK1/2 activation

Lunhua Liu1, Yili Xie, Liguang Lou

  • 1Shanghai Institute of Materia Medica, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.

European Journal of Cell Biology
|January 13, 2006
PubMed

Insights

Phosphatidylinositol 3-kinase (PI3K) differentially regulates insulin and EGF signaling pathways. PI3K is crucial for insulin-induced Ras/ERK1/2 activation but not EGF-induced activation, indicating pathway divergence.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Cancer research

Background:

  • The Ras/Raf/extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway interacts with other signaling cascades, such as phosphatidylinositol 3-kinase (PI3K)/Akt.
  • The precise role of PI3K in tyrosine kinase receptor-mediated ERK1/2 activation remains unclear.

Purpose of the Study:

  • To investigate the role of PI3K in insulin- and EGF-induced ERK1/2 activation in various cancer cell lines.
  • To elucidate the specific mechanisms by which PI3K influences Ras/ERK1/2 signaling in response to different stimuli.

Main Methods:

  • Utilized PI3K inhibitors (wortmannin, LY294002) and a protein kinase C inhibitor (chelerythrine chloride).
  • Assessed the activation of ERK1/2 and Ras in response to insulin and EGF stimulation in hepatocellular carcinoma (BEL-7402, SMMC-7721), breast cancer (MCF-7), and prostate cancer (LNCaP) cells.
  • Analyzed the divergence point of insulin-stimulated ERK1/2 and Akt signaling.

Main Results:

  • PI3K inhibitors blocked insulin-induced ERK1/2 activation but not EGF-induced activation in all tested cancer cell lines.
  • Protein kinase C inhibition did not affect insulin-induced ERK1/2 activation.
  • While both insulin and EGF require Ras activation for ERK1/2 activation, wortmannin selectively inhibited insulin-induced Ras activation.
  • Insulin-stimulated ERK1/2 and Akt signaling pathways diverge at the PI3K level.

Conclusions:

  • PI3K plays a distinct role in mediating insulin-induced Ras/ERK1/2 activation compared to EGF-induced activation.
  • The findings highlight differential regulation of signaling pathways by insulin and EGF, with implications for targeted cancer therapies.

More Related Videos

Live-Cell Förster Resonance Energy Transfer Imaging of Metabolically Regulated Akt Activation Dynamics in HepG2 Cells08:03

Live-Cell Förster Resonance Energy Transfer Imaging of Metabolically Regulated Akt Activation Dynamics in HepG2 Cells

Published on: May 23, 2025

Related Concept Videos

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...
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-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,...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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...
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...