Phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3)/Tec kinase-dependent calcium signaling pathway: a target for SHIP-mediated inhibitory signals

EMBO J. 1998 Apr 1;17(7):1961-72. doi: 10.1093/emboj/17.7.1961.

Abstract

Tec family non-receptor tyrosine kinases have been implicated in signal transduction events initiated by cell surface receptors from a broad range of cell types, including an essential role in B-cell development. A unique feature of several Tec members among known tyrosine kinases is the presence of an N-terminal pleckstrin homology (PH) domain. We directly demonstrate that phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3) interacting with the PH domain acts as an upstream activation signal for Tec kinases, resulting in Tec kinase-dependent phospholipase Cgamma (PLCgamma) tyrosine phosphorylation and inositol trisphosphate production. In addition, we show that this pathway is blocked when an SH2-containing inositol phosphatase (SHIP)-dependent inhibitory receptor is engaged. Together, our results suggest a general mechanism whereby PtdIns-3,4,5-P3 regulates receptor-dependent calcium signals through the function of Tec kinases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • Blood Proteins / genetics
  • Calcium / physiology*
  • Cell Line, Transformed
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Fibroblasts
  • Inositol Phosphates / biosynthesis
  • Isoenzymes / metabolism
  • Mutation
  • Phosphatidylinositol 3-Kinases / physiology
  • Phosphatidylinositol Phosphates / genetics
  • Phosphatidylinositol Phosphates / physiology*
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
  • Phosphoinositide-3 Kinase Inhibitors
  • Phospholipase C gamma
  • Phosphoproteins*
  • Phosphoric Monoester Hydrolases / physiology*
  • Phosphorylation
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Protein-Tyrosine Kinases / physiology
  • Rats
  • Receptors, Antigen, B-Cell / metabolism
  • Receptors, IgG / physiology
  • Sequence Homology, Amino Acid
  • Signal Transduction / physiology*
  • Type C Phospholipases / metabolism
  • Tyrosine / metabolism

Substances

  • Blood Proteins
  • Enzyme Inhibitors
  • Inositol Phosphates
  • Isoenzymes
  • Phosphatidylinositol Phosphates
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphoproteins
  • Receptors, Antigen, B-Cell
  • Receptors, IgG
  • phosphatidylinositol 3,4,5-triphosphate
  • platelet protein P47
  • Tyrosine
  • Tec protein-tyrosine kinase
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • emt protein-tyrosine kinase
  • Phosphoric Monoester Hydrolases
  • INPPL1 protein, human
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
  • Type C Phospholipases
  • Phospholipase C gamma
  • Calcium