Related Experiment Video

Updated: Aug 3, 2026

Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice
09:07

Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice

Published on: May 27, 2015

The protein tyrosine kinase syk activity is reduced by clustering the mast cell function-associated antigen

R Xu1, I Pecht

  • 1Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.

European Journal of Immunology
|July 24, 2001
PubMed

Insights

Mast cell function-associated antigen (MAFA) inhibits cell secretion by suppressing Syk kinase activity. MAFA clustering enhances SHP-2 phosphatase activity, which reduces Syk phosphorylation and activation, impacting the FcepsilonRI signaling pathway.

Area of Science:

  • Immunology
  • Cell Biology
  • Signal Transduction

Background:

  • Mast cells play a crucial role in allergic responses.
  • The type I Fcepsilon receptor (FcepsilonRI) signaling cascade is central to mast cell activation.
  • Mast cell function-associated antigen (MAFA) is known to inhibit mast cell secretion.

Purpose of the Study:

  • To elucidate the mechanism by which MAFA inhibits FcepsilonRI-mediated mast cell activation.
  • To investigate the role of protein tyrosine kinases and phosphatases in MAFA-mediated inhibition.
  • To identify the specific molecular events preceding phospholipase C activation in the FcepsilonRI pathway.

Main Methods:

  • Utilized rat mucosal-type mast cells (RBL-2H3 line).
  • Investigated protein tyrosine phosphorylation and kinase activity (Lyn, Syk) and phosphatase activity (SHP-2).
  • Employed MAFA and FcepsilonRI clustering as stimuli, assessing co-isolation of signaling molecules.

Main Results:

  • MAFA clustering reduced FcepsilonRI-induced Syk tyrosine phosphorylation and activation.
  • MAFA clustering increased SHP-2 phosphatase activity.
  • MAFA clustering enhanced co-isolation of SHP-2 with Syk and tyrosine-phosphorylated MAFA.
  • SHP-2 directly inhibited Syk activity in vitro.

Conclusions:

  • MAFA clustering inhibits mast cell secretion by suppressing Syk activity.
  • This suppression is mediated by SHP-2, which dephosphorylates and inactivates Syk.
  • MAFA influences the FcepsilonRI signaling cascade upstream of phospholipase C activation.

More Related Videos

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Related Concept Videos

Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...