Receptor Tyrosine Kinases INSR and EGFR Promote Tyrosine phosphorylation of the Signaling Coreceptor DCBLD2
Runnels, Elise
Runnels, Elise
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Abstract
Receptor tyrosine kinases (RTKs) regulate essential cellular processes including metabolism, proliferation, and survival through ligand-induced phosphorylation events that activate downstream signaling pathways. While canonical RTK signaling pathways have been extensively characterized, less is known about auxiliary proteins that modulate receptor phosphorylation dynamics. Discoidin, CUB, and LCCL domain-containing protein 2 (DCBLD2) is a single-pass transmembrane protein that functions as a signaling coreceptor and undergoes multi-site tyrosine phosphorylation. However, the relationship between DCBLD2 and receptor tyrosine kinases remains incompletely defined. This study investigated whether the receptor tyrosine kinases insulin receptor (INSR) and epidermal growth factor receptor (EGFR) regulate tyrosine phosphorylation of DCBLD2. Human HEK293 cells expressing Flag-tagged DCBLD2 were transiently transfected with INSR or EGFR, with additional conditions including DCBLD2 expression alone and stimulation with hydrogen peroxide (H?O?). DCBLD2 was isolated using anti-Flag immunoprecipitation, and phosphorylation levels were assessed by phosphotyrosine immunoblotting. Band intensities were quantified by densitometric analysis and normalized to total immunoprecipitated DCBLD2. Quantitative mass spectrometry was additionally performed to identify phosphorylation sites under each experimental condition. Co-expression of INSR or EGFR increased tyrosine phosphorylation of DCBLD2 relative to DCBLD2 alone. Mass spectrometry analysis identified multiple intracellular tyrosine residues on DCBLD2 that exhibited increased phosphorylation under receptor co-expression conditions. These findings suggest that DCBLD2 participates in RTK signaling networks and may function as a phosphorylation-dependent signaling scaffold downstream of INSR and EGFR.
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Date
1/1/2026
Student Status
Senior (Graduating in 2026)
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Poster
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Biological Science
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College of Arts and Sciences
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Life Science