Related Experiment Video

Updated: Sep 27, 2026

Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
09:40

Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum

Published on: September 20, 2011

Dok protein family members are involved in signaling mediated by the type 1 Fcepsilon receptor

Jakub Abramson1, Guido Rozenblum, Israel Pecht

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

European Journal of Immunology
|February 21, 2003
PubMed

Insights

Downstream of tyrosine kinases (Dok)-1 and Dok-2 adaptor proteins are crucial for FcepsilonRI signaling in mast cells. Overexpression of Dok-1 reduces FcepsilonRI-mediated Ras/Raf1/Erk signaling and TNF-alpha synthesis.

Area of Science:

  • Immunology
  • Cell Biology
  • Signal Transduction

Background:

  • Mast cell activation via Fc epsilon RI receptors triggers inflammatory mediator release and cellular changes.
  • The precise intracellular molecules mediating early Fc epsilon RI coupling events remain incompletely understood.

Purpose of the Study:

  • To investigate the role of Downstream of tyrosine kinases (Dok)-1 and Dok-2 adaptor proteins in the Fc epsilon RI signaling pathway in rat RBL-2H3 mast cells.

Main Methods:

  • Utilized RBL-2H3 mast cell line.
  • Investigated protein-protein interactions and phosphorylation events.
  • Assessed signaling pathway activation (Ras/Raf1/Erk) and TNF-alpha synthesis.
  • Examined the impact of Dok-1 overexpression.

Main Results:

  • Dok-1 constitutively associates with Fc epsilon RI, and both Dok-1 and Dok-2 undergo tyrosyl-phosphorylation upon receptor aggregation.
  • Dok-1 phosphorylation enhances its association with RasGAP, modulating Ras activity.
  • Overexpression of Dok-1 significantly reduces Fc epsilon RI-mediated Ras/Raf1/Erk signaling and TNF-alpha production.
  • Dok-1 and Dok-2 serve as docking sites for Nck, CrkL, and Cas, proteins involved in cytoskeletal regulation.

Conclusions:

  • Dok-1 and Dok-2 are key intracellular adaptors in the Fc epsilon RI coupling cascade.
  • These proteins play a role in modulating Ras signaling and TNF-alpha synthesis.
  • Dok-1/Dok-2 involvement in docking other signaling molecules suggests a role in Fc epsilon RI-stimulated cytoskeleton rearrangement, impacting cell adhesion, membrane ruffling, and exocytosis.

More Related Videos

In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes10:05

In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes

Published on: August 13, 2012

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration10:43

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration

Published on: May 19, 2016

Related Concept Videos

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,...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
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...