Related Experiment Video

Updated: Aug 17, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

PKCdelta and mTOR interact to regulate stress and IGF-I induced IRS-1 Ser312 phosphorylation in breast cancer cells

Amy M Mingo-Sion1, Heather A Ferguson, Erich Koller

  • 1School of Pharmacy, School of Medicine, University of Colorado Health Sciences Center, Denver, CO 80272, USA.

Breast Cancer Research and Treatment
|June 14, 2005
PubMed

Insights

Insulin Receptor Substrate-1 (IRS-1) Ser(312) phosphorylation is regulated by distinct pathways in breast cancer cells. Mammalian Target of Rapamycin (mTOR) and Protein Kinase C-delta (PKCdelta) are key mediators of this crucial signaling event.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Cancer research

Background:

  • Insulin Receptor Substrate-1 (IRS-1) is vital for insulin and IGF-I receptor signaling.
  • IRS-1 Ser(312) phosphorylation is a known mechanism for receptor signaling downregulation in diabetes.
  • The role of IRS-1 Ser(312) in cancer remains largely unexplored.

Purpose of the Study:

  • To investigate the mechanisms regulating IRS-1 Ser(312) phosphorylation in MCF-7 breast cancer cells.
  • To identify the signaling molecules involved in this regulation.
  • To understand the convergence of different signaling pathways on IRS-1.

Main Methods:

  • Utilized MCF-7 breast cancer cell line.
  • Investigated IGF-I and anisomycin-induced IRS-1 Ser(312) phosphorylation.
  • Examined the roles of PI 3-kinase, JNK, mTOR, and PKCdelta in the signaling pathways.
  • Assessed protein-protein interactions between mTOR, PKCdelta, and IRS-1.

Main Results:

  • IGF-I treatment induced PI 3-kinase-dependent IRS-1 Ser(312) phosphorylation.
  • Anisomycin stress treatment induced JNK-dependent IRS-1 Ser(312) phosphorylation.
  • Both IGF-I and anisomycin signaling converge on mTOR and PKCdelta.
  • mTOR associates with IRS-1 and is essential for Ser(312) phosphorylation.
  • PKCdelta binds to mTOR, and its activity is crucial for the phosphorylation event.

Conclusions:

  • Diverse signaling inputs (IGF-I, stress) converge on mTOR and PKCdelta to regulate IRS-1 Ser(312) phosphorylation.
  • mTOR and PKCdelta play critical roles in mediating these regulatory signals.
  • Understanding these pathways provides insights into IRS-1 regulation in breast cancer.

More Related Videos

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration11:13

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration

Published on: June 9, 2023

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...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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...