Related Experiment Video

Updated: Jun 21, 2026

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

SOCS3 expression induced by PIM2 requires PKC and PI3K signaling

Yeddula Narayana1, Kushagra Bansal, Akhauri Yash Sinha

  • 1Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India.

Molecular Immunology
|July 18, 2009
PubMed

Insights

Mycobacterial Phosphatidyl-myo-inositol dimannosides (PIM2) activate macrophages via Toll-like receptor 2 (TLR2), inducing Suppressor of cytokine signaling (SOCS) 3. This involves PI3K, PKC, and ERK1/2 signaling pathways.

Area of Science:

  • Immunology
  • Cellular Biology
  • Microbiology

Background:

  • Proinflammatory host immunity is crucial for controlling infections and developing immune memory.
  • Mycobacterial cell wall antigens play a significant role in modulating host immune responses.

Purpose of the Study:

  • To investigate the molecular mechanisms by which Phosphatidyl-myo-inositol dimannosides (PIM2), a mycobacterial antigen, induces Suppressor of cytokine signaling 3 (SOCS3) expression in macrophages.
  • To elucidate the specific signaling pathways involved in PIM2-mediated SOCS3 induction.

Main Methods:

  • Macrophage stimulation with PIM2.
  • Analysis of Toll-like receptor 2 (TLR2) and MyD88 dependency.
  • Pharmacological inhibition of key signaling molecules including PI3K, PKC, ERK1/2, p38 MAP kinase, and JNK.
  • Assessment of p65 nuclear factor-kappaB (NF-kappaB) nuclear translocation.

Main Results:

  • PIM2 triggers SOCS3 expression in macrophages in a TLR2-MyD88 dependent manner.
  • PI3K and PKC signaling pathways are involved in PIM2-induced SOCS3 expression.
  • ERK1/2 activation, dependent on PI3K/PKC, regulates NF-kappaB translocation and SOCS3 induction, while p38 and JNK are not involved.

Conclusions:

  • The PI3K-PKC-ERK1/2 signaling axis is a critical pathway for PIM2-induced SOCS3 expression in macrophages.
  • Understanding these signaling events provides insights into mycobacterial pathogenesis and host immune modulation.

More Related Videos

Primary Sjogren's Syndrome Associated with Lung Adenocarcinoma: Probing the Potential Common Pathogenic Mechanisms and Experimental Verification10:21

Primary Sjogren's Syndrome Associated with Lung Adenocarcinoma: Probing the Potential Common Pathogenic Mechanisms and Experimental Verification

Published on: September 20, 2024

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
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...
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...
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
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,...
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...