PI3K class IB pathway

Sci STKE. 2007 Oct 9;2007(407):cm2. doi: 10.1126/stke.4072007cm2.

Abstract

Class I phosphoinositide 3-kinases (PI3Ks) are well-established signal transduction enzymes that play an important role in the mechanisms by which a wide variety of cell surface receptors control several cellular functions, including cellular growth, division, survival, and movement. Class IB PI3K (also known as PI3Kgamma) allows fast-acting, heterotrimeric GTP-binding protein-coupled receptors to access this pathway. Activation of class IB PI3K results in the rapid synthesis of phosphatidylinositol-3,4,5-trisphosphate [PI(3,4,5)P3] and its dephosphorylation product, PI(3,4)P2, in the plasma membrane. These two lipid messengers bind to multiple, pleckstrin homology (PH) domain-containing effectors, which together regulate a complex signaling web downstream of receptor activation. This pathway regulates the activity of protein kinases and small guanosine triphosphatases that control cellular movement, adhesion, contraction, and secretion. Most of the ligands that have been established to activate class IB PI3K are involved in coordinating the body's response to injury and infection through the regulation of multiple cell types in the immune system and vascular lining. Mice lacking the catalytic subunit of class IB PI3K are remarkably resistant to the development of several inflammatory pathologies in mouse models of human inflammatory disease. These results suggest small molecule inhibitors of class IB PI3K may represent a novel class of therapeutic agents that may complement existing anti-inflammatory treatments.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Cell Membrane / metabolism*
  • Class Ib Phosphatidylinositol 3-Kinase
  • Disease Models, Animal
  • Humans
  • Inflammation / enzymology
  • Inflammation / metabolism
  • Inflammation / prevention & control
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphatidylinositol Phosphates / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction*

Substances

  • Anti-Inflammatory Agents
  • Isoenzymes
  • Phosphatidylinositol Phosphates
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Receptors, G-Protein-Coupled
  • phosphatidylinositol 3,4,5-triphosphate
  • phosphatidylinositol 3,4-diphosphate
  • Class Ib Phosphatidylinositol 3-Kinase
  • PIK3CG protein, human
  • Pik3cg protein, mouse