The network response to Egf is tissue-specific

Summary: Epidermal growth factor receptor (Egfr)-driven signaling regulates fundamental homeostatic processes. Dysregulated signaling via Egfr is implicated in numerous disease pathologies and distinct Egfr-associated disease etiologies are known to be tissue-specific. The molecular basis of this ti...

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Main Authors: Beatrice W. Awasthi, João A. Paulo, Deborah L. Burkhart, Ian R. Smith, Ryan L. Collins, J. Wade Harper, Steven P. Gygi, Kevin M. Haigis
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225004067
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author Beatrice W. Awasthi
João A. Paulo
Deborah L. Burkhart
Ian R. Smith
Ryan L. Collins
J. Wade Harper
Steven P. Gygi
Kevin M. Haigis
author_facet Beatrice W. Awasthi
João A. Paulo
Deborah L. Burkhart
Ian R. Smith
Ryan L. Collins
J. Wade Harper
Steven P. Gygi
Kevin M. Haigis
author_sort Beatrice W. Awasthi
collection DOAJ
description Summary: Epidermal growth factor receptor (Egfr)-driven signaling regulates fundamental homeostatic processes. Dysregulated signaling via Egfr is implicated in numerous disease pathologies and distinct Egfr-associated disease etiologies are known to be tissue-specific. The molecular basis of this tissue-specificity remains poorly understood. Most studies of Egfr signaling to date have been performed in vitro or in tissue-specific mouse models of disease, which has limited insight into Egfr signaling patterns in healthy tissues. Here, we carried out integrated phosphoproteomic, proteomic, and transcriptomic analyses of signaling changes across various mouse tissues in response to short-term stimulation with the Egfr ligand Egf. We show how both baseline and Egf-stimulated signaling dynamics differ between tissues. Moreover, we propose how baseline phosphorylation and total protein levels may be associated with clinically relevant tissue-specific Egfr-associated phenotypes. Altogether, our analyses illustrate tissue-specific effects of Egf stimulation and highlight potential links between underlying tissue biology and Egfr signaling output.
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spelling doaj-art-bb79fa4d9e044ffb98f97909ec41543c2025-08-20T02:07:40ZengElsevieriScience2589-00422025-04-0128411214610.1016/j.isci.2025.112146The network response to Egf is tissue-specificBeatrice W. Awasthi0João A. Paulo1Deborah L. Burkhart2Ian R. Smith3Ryan L. Collins4J. Wade Harper5Steven P. Gygi6Kevin M. Haigis7Center for Systems Biology, Department of Radiation Oncology, and Center for Cancer Research, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USADepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USADepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USADepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USADepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Cancer Program, Broad Institute of M.I.T. and Harvard, Cambridge, MA 02115, USADepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USADepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USADepartment of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA; Corresponding authorSummary: Epidermal growth factor receptor (Egfr)-driven signaling regulates fundamental homeostatic processes. Dysregulated signaling via Egfr is implicated in numerous disease pathologies and distinct Egfr-associated disease etiologies are known to be tissue-specific. The molecular basis of this tissue-specificity remains poorly understood. Most studies of Egfr signaling to date have been performed in vitro or in tissue-specific mouse models of disease, which has limited insight into Egfr signaling patterns in healthy tissues. Here, we carried out integrated phosphoproteomic, proteomic, and transcriptomic analyses of signaling changes across various mouse tissues in response to short-term stimulation with the Egfr ligand Egf. We show how both baseline and Egf-stimulated signaling dynamics differ between tissues. Moreover, we propose how baseline phosphorylation and total protein levels may be associated with clinically relevant tissue-specific Egfr-associated phenotypes. Altogether, our analyses illustrate tissue-specific effects of Egf stimulation and highlight potential links between underlying tissue biology and Egfr signaling output.http://www.sciencedirect.com/science/article/pii/S2589004225004067molecular biologybioengineeringsystems biology
spellingShingle Beatrice W. Awasthi
João A. Paulo
Deborah L. Burkhart
Ian R. Smith
Ryan L. Collins
J. Wade Harper
Steven P. Gygi
Kevin M. Haigis
The network response to Egf is tissue-specific
iScience
molecular biology
bioengineering
systems biology
title The network response to Egf is tissue-specific
title_full The network response to Egf is tissue-specific
title_fullStr The network response to Egf is tissue-specific
title_full_unstemmed The network response to Egf is tissue-specific
title_short The network response to Egf is tissue-specific
title_sort network response to egf is tissue specific
topic molecular biology
bioengineering
systems biology
url http://www.sciencedirect.com/science/article/pii/S2589004225004067
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