Related Experiment Video

Updated: Jul 20, 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

PTEN and SHIP2 phosphoinositide phosphatases as negative regulators of insulin signalling

Manlio Vinciguerra1, Michelangelo Foti

  • 1Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Archives of Physiology and Biochemistry
|August 26, 2006
PubMed

Insights

Insulin resistance drives type II diabetes. Negative regulators like PTEN and SHIP2 are key targets for reducing this resistance and treating diabetes.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Background:

  • Insulin resistance in peripheral tissues is a primary cause of type II diabetes mellitus.
  • Understanding intracellular signaling pathways is crucial for elucidating insulin resistance mechanisms.
  • Negative regulators of insulin signaling are potential therapeutic targets.

Purpose of the Study:

  • To review major intracellular signaling pathways activated by insulin.
  • To discuss the negative regulation of these pathways.
  • To focus on the role of PTEN and SHIP2 in insulin resistance and type II diabetes.

Main Methods:

  • Review of current literature on insulin signaling pathways.
  • Analysis of genetic and biochemical data.
  • Discussion of phosphoinositide phosphatases PTEN and SHIP2.

Main Results:

  • Insulin resistance is linked to dysregulated intracellular signaling.
  • PTEN and SHIP2 are identified as key negative modulators of insulin signaling.
  • These phosphatases play a significant role in insulin resistance and type II diabetes.

Conclusions:

  • PTEN and SHIP2 are critical in modulating insulin signaling.
  • Targeting PTEN and SHIP2 may offer therapeutic strategies for type II diabetes.
  • Further research into these negative regulators is warranted.

More Related Videos

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes09:40

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

Published on: September 28, 2018

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...
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...
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...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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...