Low affinity Fc gamma receptors on murine macrophages: mitogen-activated protein kinase activation and AP-1 DNA

M J Cote-Vélez1, E Ortega, A Ortega

  • 1Departamento de Genética y Biología Molecular Centro de Investagacion y de Estudios Avanzados del IPN 2508, C.P. México, Mexico.

Immunology Letters
|June 16, 1999
PubMed

Insights

Mouse macrophages activate signaling pathways upon Fc receptor stimulation, leading to increased mitogen-activated protein kinase (MAPK) and activator protein 1 (AP-1) DNA binding. These findings illuminate Fc gamma receptor cross-linking in gene expression regulation.

Area of Science:

  • Immunology
  • Cell Signaling
  • Molecular Biology

Background:

  • Mouse macrophage cell lines like J774 possess Fc receptors for IgG2a immune complexes.
  • Fc receptor engagement initiates signal transduction pathways from the cell surface to the nucleus.

Purpose of the Study:

  • To investigate the specific signaling pathways activated by Fc gamma receptor (FcγR) cross-linking in macrophages.
  • To elucidate the role of protein kinase C (PKC) in FcγR-mediated signaling.

Main Methods:

  • Stimulation of J774 macrophage cell lines with IgG2a immune complexes.
  • Analysis of mitogen-activated protein kinase (MAPK) activation.
  • Assessment of activator protein 1 (AP-1) DNA binding activity.
  • Inhibition studies using protein kinase C (PKC) inhibitors.

Main Results:

  • FcγR stimulation activates MAPK signaling.
  • AP-1 DNA binding increases significantly upon FcγR cross-linking.
  • PKC inhibition only partially blocks these signaling events, indicating parallel pathways.

Conclusions:

  • FcγR cross-linking triggers distinct signaling cascades that converge at or upstream of the MAPK pathway.
  • These pathways are crucial for FcγR-mediated gene expression regulation in macrophages.

Related Concept Videos

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...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
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...
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...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...