Dissecting the Role of Y4474 and Y4508 on CD91 in AXL/Fgr Binding and Cancer Immunosurveillance Signaling

Authors

  • Keya Shah University of Pittsburgh

DOI:

https://doi.org/10.5195/pur.2026.154

Abstract

The recognition of danger-associated molecular patterns (DAMPs) released by tumor cells is a critical early step in recognizing emerging tumors, and these include heat shock proteins (HSPs) that bind to receptors like CD91 on immune cells. In this study, we investigated whether specific tyrosine residues within the CD91 β chain are essential for CD91-directed cancer immunosurveillance signaling. We used CRISPR-Cas9 gene editing to investigate these tyrosines by replacing them with phenylalanine. Our results revealed distinct and residue-specific effects on downstream signaling, the most notable being Y2F clone 4, which contained mutations in the NPxY phosphotyrosine-binding motif, a crucial docking site for signaling proteins. This clone showed significantly reduced cytokine production in response to HSP stimulation, confirming that this phosphotyrosine-binding domain is important for CD91-mediated signal transduction and that these CD91 tyrosine residues are essential for CD91 signaling and cytokine induction. By establishing the functional significance of specific tyrosine residues within CD91, this study deepens our understanding of certain molecular mechanisms underlying cancer immunosurveillance, and allows for further research regarding immunotherapeutic approaches that target the HSP-CD91 axis.

Author Biography

Keya Shah, University of Pittsburgh

Keya Shah is a sophomore on the pre-medical track at the University of Pittsburgh majoring in Biological Sciences with a minor in Chemistry and a certificate in the Conceptual Foundations of Medicine.

References

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Harkness, James Trey, Devanshi A. Nayak, Abigail L. Sedlacek, Richard Cattley, William F. Hawse, Simon C. Watkins, and Robert J. Binder. “CD91-Mediated Reprogramming of DCS by Immunogenic Heat Shock Proteins Requires the Kinases Axl and FGR.” Cell Communication and Signaling 22, no. 1 (December 18, 2024). https://doi.org/10.1186/s12964-024-01901-6.

Harkness, Trey J. F., Abigail L Sedlacek, Keya Shah, Alyssa Juergens, Joel Greenberger, Amitava Mukherjee, A, and Robert J. Binder. “Disruption of CD91 association with AXL and Fgr abrogates HSP-mediated signaling and cancer immunosurveillance.” OncoImmunology, (2025) (in press).

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Published

2026-03-27

How to Cite

Shah, K. (2026). Dissecting the Role of Y4474 and Y4508 on CD91 in AXL/Fgr Binding and Cancer Immunosurveillance Signaling. Pittsburgh Undergraduate Review, 5(1). https://doi.org/10.5195/pur.2026.154

Issue

Vol. 5 No. 1 (2026): Pittsburgh Undergraduate Review

Section

Research

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Copyright (c) 2026 Keya Shah

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