Question

Which of the following signaling pathways will be upregulated in microglia after stimulation with interferon-g (IFN- \(\gamma\) ? a. cAMP-PKA pathway b. cGMP-PKG pathway c. JAK-STAT pathway d. PI-3 kinase-Akt pathway e. TLR4 pathway

Short answer

Answer: The JAK-STAT pathway is upregulated in microglia after stimulation with interferon-γ (IFN-γ). This is because IFN-γ binds to its receptor on the cell surface, leading to the activation of receptor-associated JAK proteins. These proteins phosphorylate STAT molecules, which dimerize, translocate to the nucleus, and regulate the transcription of target genes. In microglia, this process leads to an upregulation of pro-inflammatory genes and the immune response.

Step-by-step solution

Analyze the provided options

To find the signaling pathway that will be upregulated in microglia after stimulation with IFN-γ, let's briefly analyze each pathway: a. cAMP-PKA pathway b. cGMP-PKG pathway c. JAK-STAT pathway d. PI-3 kinase-Akt pathway e. TLR4 pathway

Choose the correct pathway

Interferon-γ (IFN-γ) is known to activate the JAK-STAT signaling pathway. This pathway is involved in the regulation of cellular responses like inflammation, proliferation, and apoptosis. Particularly in microglia, IFN-γ causes an increase in the activation of JAK and STAT proteins, leading to pro-inflammatory gene expression. Thus, the correct answer is: c. JAK-STAT pathway

Explain the rationale behind the choice

The JAK-STAT pathway is selected because IFN-γ binds to its receptor on the cell surface, leading to the activation of receptor-associated JAK (Janus Kinases) proteins. Afterwards, these proteins phosphorylate STAT (Signal Transducers and Activators of Transcription) molecules. The phosphorylated STAT proteins dimerize and translocate to the nucleus, where they bind to specific DNA sequences and regulate the transcription of target genes. In microglia, this process leads to an upregulation of pro-inflammatory genes and the immune response.