Open AccessSMOC Binds to Pro-EGF, but Does Not Induce Erk Phosphorylation via the EGFR
Author(s) -
J. Terrig Thomas,
Lina Chhuy-Hy,
Kristin Andrykovich,
Malcolm Moos
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0154294
Subject(s) - mapk/erk pathway , epidermal growth factor , phosphorylation , microbiology and biotechnology , epidermal growth factor receptor , extracellular , signal transduction , kinase , chemistry , receptor , biology , biochemistry
In an attempt to identify the cell-associated protein(s) through which SMOC ( S ecreted Mo dular C alcium binding protein) induces mitogen-activated protein kinase (MAPK) signaling, the epidermal growth factor receptor (EGFR) became a candidate. However, although in 32D/EGFR cells, the EGFR was phosphorylated in the presence of a commercially available human SMOC-1 (hSMOC-1), only minimal phosphorylation was observed in the presence of Xenopus SMOC-1 ( X SMOC-1) or human SMOC-2. Analysis of the commercial hSMOC-1 product demonstrated the presence of pro-EGF as an impurity. When the pro-EGF was removed, only minimal EGFR activation was observed, indicating that SMOC does not signal primarily through EGFR and its receptor remains unidentified. Investigation of SMOC/pro-EGF binding affinity revealed a strong interaction that does not require the C-terminal extracellular calcium-binding (EC) domain of SMOC or the EGF domain of pro-EGF. SMOC does not appear to potentiate or inhibit MAPK signaling in response to pro-EGF, but the interaction could provide a mechanism for retaining soluble pro-EGF at the cell surface.