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Updated: Feb 9, 2026

Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy
Published on: September 11, 2015
Papillomavirus E2 protein is regulated by specific fibroblast growth factor receptors
Marsha DeSmet1, Sriramana Kanginakudru1, Leny Jose1
1Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA.
Abstract:
The papillomavirus (PV) E2 protein activates transcription and replication by recruiting cellular proteins and the E1 DNA helicase to their binding sites in the viral genome. We recently demonstrated that phosphorylation of tyrosine 102 in the bovine papillomavirus (BPV-1) E2 protein restricts these activities and that fibroblast growth factor receptor-3 (FGFR3) tyrosine kinase binds PV E2. Expression of FGFR3 decreased viral replication with both wild-type and the phenylalanine substitution at position 102, inferring that another kinase targets Y102. Here we tested FGFR- 1, -2 and -4 for association with PV E2 proteins. FGFR2 but not FGFR1 or FGFR4 co-immunoprecipitated with BPV-1 E2. We found that FGFR2 suppressed replication but did not depend on phosphorylation of BPV-1 Y102. HPV-16 and -31 E2 interacted with FGFR1, -2, and -4. These results imply that the expression and activity of FGF receptors in epithelial cells can regulate the function of E2 in viral replication.
Insights
Fibroblast growth factor receptors (FGFRs) interact with papillomavirus (PV) E2 proteins, influencing viral replication. Different FGFRs associate with various PV types, suggesting a role in regulating viral activity in epithelial cells.
Area of Science:
- Virology
- Molecular Biology
- Cellular Biology
Background:
- The papillomavirus (PV) E2 protein is crucial for viral transcription and replication.
- Phosphorylation of tyrosine 102 in bovine papillomavirus (BPV-1) E2 by fibroblast growth factor receptor-3 (FGFR3) inhibits these functions.
- FGFR3's effect on viral replication suggested another kinase targets Y102.
Purpose of the Study:
- To investigate the association of FGFR1, FGFR2, and FGFR4 with PV E2 proteins.
- To determine if FGFR2-mediated suppression of viral replication depends on Y102 phosphorylation.
- To explore interactions between human papillomavirus (HPV) E2 proteins and FGFRs.
Main Methods:
- Co-immunoprecipitation assays to test protein interactions.
- Replication assays to assess viral activity.
- Analysis of interactions between different HPV types (HPV-16, HPV-31) and FGFRs.
Main Results:
- FGFR2, but not FGFR1 or FGFR4, co-immunoprecipitated with BPV-1 E2.
- FGFR2 suppressed BPV-1 replication independently of Y102 phosphorylation.
- HPV-16 and HPV-31 E2 proteins interacted with FGFR1, FGFR2, and FGFR4.
Conclusions:
- FGF receptors exhibit differential interactions with PV E2 proteins from various viral types.
- FGFR2 can regulate PV replication through mechanisms not solely dependent on Y102 phosphorylation.
- FGFR expression and activity in epithelial cells may control PV E2 function and viral replication.
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