Related Experiment Video

Updated: Aug 8, 2026

Investigating Mast Cell Secretory Granules; from Biosynthesis to Exocytosis
16:01

Investigating Mast Cell Secretory Granules; from Biosynthesis to Exocytosis

Published on: January 26, 2015

Molecular mechanisms of CD200 inhibition of mast cell activation

Shuli Zhang1, Holly Cherwinski, Jonathon D Sedgwick

  • 1DNAX Research Institute, Palo Alto, CA 94304, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|November 24, 2004
PubMed

Insights

CD200 receptor (CD200R) engagement inhibits myeloid cell activation by blocking Ras/MAPK pathways. This novel mechanism involves Dok1/Dok2 adapter proteins, leading to reduced mast cell degranulation and cytokine production.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • CD200 and its receptor CD200R are type I membrane glycoproteins involved in immune regulation.
  • CD200R engagement inhibits myeloid cell activation, but the underlying molecular mechanism is unknown.
  • CD200R lacks a typical ITIM motif, differentiating it from other inhibitory receptors.

Purpose of the Study:

  • To elucidate the signaling pathways by which CD200R inhibits myeloid cell activation.
  • To investigate the role of CD200R in controlling degranulation and cytokine production in mouse bone marrow-derived mast cells.

Main Methods:

  • Examined CD200R signaling pathways in mouse bone marrow-derived mast cells upon ligand binding.
  • Investigated tyrosine phosphorylation of CD200R and its association with adapter proteins.
  • Analyzed the recruitment of SHIP and RasGAP to CD200R signaling complexes.
  • Assessed the impact of CD200R engagement on Ras/MAPK pathway activation (ERK, JNK, p38).

Main Results:

  • CD200R engagement leads to tyrosine phosphorylation and binding of Dok1 and Dok2 adapter proteins.
  • Dok1 recruits SHIP, and both Dok1 and Dok2 recruit RasGAP, inhibiting Ras/MAPK pathways.
  • Activation of ERK, JNK, and p38 MAPK is suppressed by CD200R engagement.
  • Mast cell degranulation and cytokine production are inhibited, correlating with reduced MAPK activation.

Conclusions:

  • CD200R utilizes a novel inhibitory pathway involving Dok1/Dok2, SHIP, and RasGAP to modulate mast cell function.
  • This pathway suppresses Ras/MAPK signaling, leading to the inhibition of mast cell degranulation and cytokine release.
  • The findings provide insights into how CD200R engagement regulates myeloid cell function in vivo.

More Related Videos

Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice09:07

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

Published on: May 27, 2015

Isolation of Peritoneum-derived Mast Cells and Their Functional Characterization with Ca2+-imaging and Degranulation Assays11:31

Isolation of Peritoneum-derived Mast Cells and Their Functional Characterization with Ca2+-imaging and Degranulation Assays

Published on: July 4, 2018

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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...
Immunoglobulin-like Cell Adhesion Molecules01:31

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...