Differential regulation of phospholipase Cgamma subtypes through FcepsilonRI, high affinity IgE receptor

Biochem Biophys Res Commun. 2004 Dec 3;325(1):117-23. doi: 10.1016/j.bbrc.2004.09.216.

Abstract

The high affinity IgE receptor (FcepsilonRI) usually exists as a tetramer composed of alphabetagamma2 subunits. The COOH-tail of beta and gamma subunits contains consensus sequence termed 'immunoreceptor tyrosine-based activation motif' (ITAM). Tyrosine phosphorylated ITAM interacts with signaling proteins that contain the Src homology domain, forming a main amplifying and signaling route for FcepsilonRI. Unlike the COOH-tail, the functional role of NH(2)-tail of beta subunit in the signaling of FcepsilonRI is not clear because it lacks the ITAM sequences. To study the roles of NH(2)-tail of beta subunit, the cDNA library of RBL-2H3 cells was screened by yeast two-hybrid assay, and the NH(2)-tail of the beta subunit was found to interact with phospholipase Cgamma2 (PLCgamma2) but not with PLCgamma1. Since both PLCgamma1 and PLCgamma2 are expressed in RBL-2H3 cells and they possess identical cellular functions, the functional meaning of the protein-protein interaction between PLCgamma2 and NH(2)-tail of beta subunit was studied by comparing the regulatory pathways that control the FcepsilonRI-mediated tyrosine phosphorylation of the two enzymes. Our study shows that PI3-kinase and PMA-sensitive PKCs were required exclusively for the FcepsilonRI-mediated tyrosine phosphorylation of PLCgamma1. Also the FcepsilonRI-mediated tyrosine phosphorylation of PLCgamma1 was more sensitive to the inhibitors of Src and Syk kinases. These results therefore suggest that PLCgamma1 is involved in dynamic regulation of protein kinase C activity and inositol triphosphate levels in response to cellular needs. In contrast, PLCgamma2, through continuous interaction with the NH(2)-tail of beta subunit, co-localizes with FcepsilonRI in the same signaling domain, and maintains the basal cellular PLC activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Gene Expression Regulation, Enzymologic*
  • Immunoglobulin E / metabolism*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phospholipase C gamma
  • Phosphorylation
  • Protein Kinase C / metabolism
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Rats
  • Receptors, IgE / genetics
  • Receptors, IgE / metabolism*
  • Signal Transduction / physiology
  • Tetradecanoylphorbol Acetate / metabolism
  • Two-Hybrid System Techniques
  • Type C Phospholipases / genetics
  • Type C Phospholipases / metabolism*
  • Tyrosine / metabolism

Substances

  • Isoenzymes
  • Protein Subunits
  • Receptors, IgE
  • Immunoglobulin E
  • Tyrosine
  • Phosphatidylinositol 3-Kinases
  • Protein Kinase C
  • Type C Phospholipases
  • Phospholipase C gamma
  • Tetradecanoylphorbol Acetate