A Novel Tyrosine Kinase Axis in Innate Immune Signaling

Authors

• Santanu Das, University of Kentucky
• Pracheta Sengupta, University of KentuckyFollow
• Manoj Veleeparambil, University of KentuckyFollow
• Saurabh Chattopadhyay, University of KentuckyFollow

Abstract

Tyrosine phosphorylation has emerged as a central regulatory mechanism in innate immunity. Building on our recent studies that Syk and EGFR sequentially phosphorylate TLR9 to fully activate it, we discuss how similar mechanisms operate across other Toll-like receptors and the cytosolic DNA sensor STING. Evidence from complementary systems reveals that receptor and nonreceptor tyrosine kinases, including Src-family kinases, Syk, BTK, and EGFR, form an integrated signaling network that triggers receptor activation, trafficking, and downstream gene expression. Scavenger receptors such as SR-A further drive this kinase cascade by coordinating viral recognition to TLR activation. These observations reveal a novel ‘tyrosine kinase axis’ that connects nucleic acid sensing to spatially controlled innate immune signaling and highlight new opportunities to modulate innate immunity through tyrosine kinase regulation.

Document Type

Article

Publication Date

2026

Notes/Citation Information

© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.

Digital Object Identifier (DOI)

https://doi.org/10.3390/v18010010

Funding Information

Research in the authors’ laboratory is funded by National Institutes of Health grants AI155545 (S.C.), AI165521 (S.C.), and AA027456 (S.C.).

Repository Citation

Das, Santanu; Sengupta, Pracheta; Veleeparambil, Manoj; and Chattopadhyay, Saurabh, "A Novel Tyrosine Kinase Axis in Innate Immune Signaling" (2026). Microbiology, Immunology, and Molecular Genetics Faculty Publications. 207.
https://uknowledge.uky.edu/microbio_facpub/207