Related Experiment Video

Updated: Mar 19, 2026

A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces
07:55

A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces

Published on: January 7, 2020

7.9K

Sprouty2 modulates NF-κB signaling by sequestering the phosphatase PP2Ac in LPS-stimulated macrophages

Anand Sripada1, Rangati Varma1, Kapil Sirohi1

  • 1Division of Allergy and Immunology, Department of Medicine, National Jewish Health, Denver, CO, United States.

Journal of Immunology (Baltimore, Md. : 1950)
|March 18, 2026
PubMed

Insights

Sprouty2 (Spry2) enhances immune responses by binding to PP2Ac, a negative regulator, in macrophages stimulated by lipopolysaccharide (LPS). This Spry2-PP2Ac interaction boosts NF-κB activation and cytokine production, crucial for innate immunity.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • The adapter protein Sprouty2 (Spry2) is implicated in various signaling pathways.
  • Its precise role in lipopolysaccharide (LPS)/Toll-like receptor 4 (TLR4)-mediated signaling remains unclear.

Purpose of the Study:

  • To elucidate the function of Spry2 in LPS/TLR4-induced signaling in macrophages.
  • To investigate the molecular mechanisms by which Spry2 regulates NF-κB activation.

Main Methods:

  • Utilized bone marrow-derived macrophages (BMDM) from wild-type and Spry2-deficient mice.
  • Stimulated macrophages with LPS and analyzed NF-κB and MAPK signaling pathways.
  • Investigated protein-protein interactions using co-immunoprecipitation and assessed protein phosphorylation.

Main Results:

  • Spry2 deficiency impaired LPS-induced NF-κB activation and cytokine production in BMDM.
  • Spry2 positively regulates NF-κB by sequestering the phosphatase PP2Ac.
  • Spry2 phosphorylation upon LPS stimulation enhances its association with PP2Ac, promoting p65 nuclear translocation and cytokine secretion.

Conclusions:

  • Sprouty2 plays a novel, positive regulatory role in LPS/TLR4-mediated NF-κB activation.
  • Spry2 modulates innate immune responses by controlling PP2Ac activity and subsequent p65 signaling.
  • Targeting Spry2 may offer therapeutic strategies for inflammatory conditions.
Keywords:
NF-κB signaling pathwaySprouty2TLR4

More Related Videos

Intraductal Injection of LPS as a Mouse Model of Mastitis: Signaling Visualized via an NF-κB Reporter Transgenic08:51

Intraductal Injection of LPS as a Mouse Model of Mastitis: Signaling Visualized via an NF-κB Reporter Transgenic

Published on: September 4, 2012

20.0K
NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells10:57

NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells

Published on: January 12, 2020

11.3K

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...
10.2K
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

2.4K
Gene Regulation During Sporulation01:17

Gene Regulation During Sporulation

Sporulation is a complex developmental process that allows certain Gram-positive bacteria, such as Bacillus subtilis and Clostridium species, to survive extreme environmental conditions. This process is tightly regulated by a series of signaling cascades and transcriptional controls, ensuring the formation of a highly resistant endospore.Sporulation is triggered by unfavorable conditions, such as nutrient depletion, and is governed by a phosphorelay system. One of the sensor kinases, such as...
626
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.4K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.2K
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,...
9.1K