52. Interferon α, β and γare cytokines produced and secreted by animal cells after infection by viruses. which of the following statements about interferons is INCORRECT?
(1) When mammalian cells are incubated With different interferons. activation of STATS (Signal Transducer Activators of Transcription) links stimulation of cell surface receptors With gene expression.
(2) Increase in the expression of genes after addition of IFNα results only after activation of the interferon. stimulated response element (ISRE),
(3) The receptors Of all three interferons belong to the lgsuperfamily of receptors and do not lead to downstream phosphorylation events.
(4) An important feature of interferon-STAT signaling pathway is its specificity: each type of interferon induces transcription of a unique subset of genes.

Introduction

Interferons (IFNs) are crucial cytokines produced by animal cells in response to viral infections. They orchestrate complex signaling cascades to induce antiviral states and modulate the immune response. IFN signaling primarily occurs via the JAK-STAT pathway, linking receptor engagement to transcriptional activation of antiviral genes.

Correct Statements About Interferon Signaling

1. STAT Activation Links Receptors to Gene Expression: IFNs bind their cell surface receptors, triggering activation of JAK kinases, which phosphorylate STATs (Signal Transducers and Activators of Transcription). Activated STATs dimerize and translocate to the nucleus to regulate gene expression.​

2. Gene Expression Induced Via ISRE: IFN-α and IFN-β signal through formation of the ISGF3 complex (STAT1:STAT2:IRF9), which binds the interferon-stimulated response element (ISRE) in DNA, leading to transcription of specific interferon-stimulated genes (ISGs).​

3. Specificity of Interferon-STAT Signaling: Each interferon type activates distinct STAT dimers or complexes, thus inducing unique gene subsets, contributing to signaling specificity.​

The Incorrect Statement

“The receptors of all three interferons belong to the Ig superfamily of receptors and do not lead to downstream phosphorylation events.”

Why This Is Incorrect: Interferon receptors belong to the cytokine receptor superfamily, often class II cytokine receptors, not solely the Ig superfamily. Critically, binding of interferons to their receptors leads to activation of receptor-associated Janus kinases (JAKs), which phosphorylate receptor cytoplasmic domains and STAT proteins, constituting essential downstream phosphorylation events required for signal propagation.​

Thus, the incorrect statement is:

(3) The receptors of all three interferons belong to the Ig superfamily of receptors and do not lead to downstream phosphorylation events.

Summary Table