Expression of macrophage asialoglycoprotein-binding protein is induced through MAPK classical pathway

R Katsuyama1, A Morioka, S Oka

  • 1Department of Biological Chemistry and CREST (Core Research for Educational Science and Technology) Project, Japan Science and Technology Corporation, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan.

Insights

Macrophage asialoglycoprotein-binding protein (M-ASGP-BP) mRNA expression is induced during macrophage differentiation. Protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) pathways mediate this M-ASGP-BP induction.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Macrophage asialoglycoprotein-binding protein (M-ASGP-BP) is a Gal/GalNAc-specific lectin.
  • M-ASGP-BP functions as an endocytosis receptor.
  • M-ASGP-BP mRNA expression is induced during macrophage differentiation from bone marrow cells.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying M-ASGP-BP mRNA induction during macrophage differentiation.
  • To utilize U937 cells as a model system for studying M-ASGP-BP gene regulation.

Main Methods:

  • U937 cells were treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) to induce differentiation.
  • The effects of protein kinase C (PKC) inhibitors (calphostin C, staurosporine) and mitogen-activated protein kinase (MAPK) inhibitors (PD98059, SB202190) on M-ASGP-BP mRNA expression were assessed.

Main Results:

  • TPA treatment rapidly induced M-ASGP-BP mRNA expression in U937 cells within 6 hours.
  • PKC inhibitors completely blocked TPA-induced M-ASGP-BP mRNA expression.
  • The MAPK inhibitor PD98059, but not SB202190, inhibited M-ASGP-BP mRNA expression, suggesting involvement of the classical MAPK pathway.

Conclusions:

  • M-ASGP-BP mRNA expression during macrophage differentiation is mediated by the activation of PKC.
  • The classical MAPK pathway is also involved in the induction of M-ASGP-BP mRNA.
  • These findings elucidate key signaling pathways regulating M-ASGP-BP expression in differentiating macrophages.

Related Concept Videos

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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...