Roles of PLC-beta2 and -beta3 and PI3Kgamma in chemoattractant-mediated signal transduction

Science. 2000 Feb 11;287(5455):1046-9. doi: 10.1126/science.287.5455.1046.

Abstract

The roles of phosphoinositide 3-kinase (PI3K) and phospholipase C (PLC) in chemoattractant-elicited responses were studied in mice lacking these key enzymes. PI3Kgamma was required for chemoattractant-induced production of phosphatidylinositol 3,4,5-trisphosphate [PtdIns (3,4,5)P3] and has an important role in chemoattractant-induced superoxide production and chemotaxis in mouse neutrophils and in production of T cell-independent antigen-specific antibodies composed of the immunoglobulin lambda light chain (TI-IglambdaL). The study of the mice lacking PLC-beta2 and -beta3 revealed that the PLC pathways have an important role in chemoattractant-mediated production of superoxide and regulation of protein kinases, but not chemotaxis. The PLC pathways also appear to inhibit the chemotactic activity induced by certain chemoattractants and to suppress TI-IglambdaL production.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Chemokine CCL4
  • Chemotactic Factors / pharmacology*
  • Chemotaxis, Leukocyte / physiology*
  • Immunoglobulin lambda-Chains / biosynthesis
  • Isoenzymes / metabolism*
  • Macrophage Inflammatory Proteins / pharmacology
  • Mice
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophil Infiltration
  • Neutrophils / metabolism
  • Neutrophils / physiology*
  • Peritonitis / immunology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphatidylinositol Phosphates / metabolism
  • Phospholipase C beta
  • Phosphorylation
  • Signal Transduction*
  • Skin Ulcer / pathology
  • Superoxides / metabolism
  • Type C Phospholipases / metabolism*

Substances

  • Chemokine CCL4
  • Chemotactic Factors
  • Immunoglobulin lambda-Chains
  • Isoenzymes
  • Macrophage Inflammatory Proteins
  • Phosphatidylinositol Phosphates
  • phosphatidylinositol 3,4,5-triphosphate
  • Superoxides
  • N-Formylmethionine Leucyl-Phenylalanine
  • Phosphatidylinositol 3-Kinases
  • Type C Phospholipases
  • Phospholipase C beta
  • Plcb2 protein, mouse
  • Plcb3 protein, mouse