Roles of a conserved family of adaptor proteins, Lnk, SH2-B, and APS, for mast cell development, growth, and functions: APS-deficiency causes augmented degranulation and reduced actin assembly

Biochem Biophys Res Commun. 2004 Mar 5;315(2):356-62. doi: 10.1016/j.bbrc.2004.01.060.

Abstract

Lnk, SH2-B, and APS form a conserved adaptor protein family. All of those proteins are expressed in mast cells and their possible functions in signaling through c-Kit or FcRI have been speculated. To investigate roles of Lnk, SH2-B or APS in mast cells, we established IL-3-dependent mast cells from Ink-/-, SH2-B-/-, and APS -/- mice. IL-3-dependent growth of those cells was comparable. Proliferation or adhesion mediated by c-Kit as well as degranulation induced by cross-linking FcRI were normal in the absence of Lnk or SH2-B. In contrast, APS-deficient mast cells showed augmented degranulation after cross-linking FcRI compared to wild-type cells, while c-Kit-mediated proliferation and adhesion were kept unaffected. APS-deficient mast cells showed reduced actin assembly at steady state, although their various intracellular responses induced by cross-linking FcRI were indistinguishable compared to wild-type cells. Our results suggest potential roles of APS in controlling actin cytoskeleton and magnitude of degranulation in mast cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Actins / metabolism*
  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Calcium / metabolism
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Cell Adhesion
  • Cell Division
  • Cell Movement
  • Cell Separation
  • Cell Survival
  • Cross-Linking Reagents / pharmacology
  • Cytokines / metabolism
  • Cytoskeleton / metabolism
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Flow Cytometry
  • Immunoblotting
  • Immunohistochemistry
  • Interleukin-3 / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Mast Cells / cytology*
  • Mast Cells / metabolism
  • Membrane Proteins
  • Mice
  • Mice, Transgenic
  • Protein Binding
  • Protein-Tyrosine Kinases / metabolism
  • Proteins / chemistry
  • Proteins / metabolism
  • Proteins / physiology*
  • Proto-Oncogene Proteins c-kit / metabolism
  • Receptors, Cytokine / metabolism
  • Receptors, IgE / chemistry
  • Signal Transduction
  • Thiazoles / pharmacology
  • Thiazolidines
  • Time Factors

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • Bridged Bicyclo Compounds, Heterocyclic
  • Carrier Proteins
  • Cross-Linking Reagents
  • Cytokines
  • Interleukin-3
  • Intracellular Signaling Peptides and Proteins
  • Lnk protein, mouse
  • Membrane Proteins
  • Proteins
  • Receptors, Cytokine
  • Receptors, IgE
  • SH2B1 protein, human
  • SH2B1 protein, rat
  • SH2B3 protein, human
  • Sh2b2 protein, mouse
  • Sh2b2 protein, rat
  • Sh2bpsm1 protein, mouse
  • Thiazoles
  • Thiazolidines
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-kit
  • latrunculin A
  • Calcium