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SMOC Binds to Pro-EGF, but Does Not Induce Erk Phosphorylation via the EGFR

J Terrig Thomas1, Lina Chhuy-Hy1, Kristin R Andrykovich1

  • 1FDA/Center for Biologics Evaluation and Research, Division of Cellular and Gene Therapies Office of Cellular, Tissue, and Gene Therapies, Silver Spring, MD, United States of America.

Plos One
|April 22, 2016
PubMed

Insights

Secreted Modular Calcium binding protein (SMOC) does not primarily signal through the epidermal growth factor receptor (EGFR). Researchers found SMOC binds to pro-Epidermal Growth Factor (pro-EGF), potentially retaining it on cell surfaces.

Area of Science:

  • Cell signaling
  • Molecular biology
  • Protein interactions

Background:

  • Secreted Modular Calcium binding protein (SMOC) is implicated in mitogen-activated protein kinase (MAPK) signaling.
  • The epidermal growth factor receptor (EGFR) was investigated as a potential mediator of SMOC-induced signaling.

Purpose of the Study:

  • To identify the cell-associated protein responsible for SMOC-induced MAPK signaling.
  • To investigate the interaction between SMOC and pro-Epidermal Growth Factor (pro-EGF).

Main Methods:

  • Phosphorylation assays in 32D/EGFR cells using various SMOC proteins.
  • Analysis of commercial SMOC-1 for impurities.
  • Binding affinity studies between SMOC and pro-EGF.

Main Results:

  • Commercial human SMOC-1 (hSMOC-1) induced EGFR phosphorylation, but this was attributed to a pro-Epidermal Growth Factor (pro-EGF) impurity.
  • Xenopus SMOC-1 (XSMOC-1) and human SMOC-2 showed minimal EGFR activation.
  • SMOC exhibited strong binding to pro-EGF, independent of specific domains.
  • SMOC did not significantly alter pro-EGF's effect on MAPK signaling.

Conclusions:

  • SMOC does not primarily signal through EGFR; its specific receptor remains unidentified.
  • SMOC interacts with pro-EGF, potentially regulating its cell surface localization.
  • This interaction may influence pro-EGF availability without directly modulating MAPK signaling pathways.

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