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Roles of the third Ig‐like domain of Necl‐5/ PVR and the fifth Ig‐like domain of the PDGF receptor in its signaling
Author(s) -
Ueda Yuki,
Kedashiro Shin,
Maruoka Masahiro,
Mizutani Kiyohito,
Takai Yoshimi
Publication year - 2018
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12564
Subject(s) - platelet derived growth factor receptor , biology , receptor , signal transduction , microbiology and biotechnology , tyrosine phosphorylation , growth factor , biochemistry
The immunoglobulin (Ig)‐like cell adhesion molecule nectin‐like molecule (Necl)‐5/poliovirus receptor is up‐regulated in many types of cancer cells and implicated in their abnormally enhanced cell proliferation and movement. We previously showed that Necl‐5 cis ‐interacts with the platelet‐derived growth factor ( PDGF ) receptor β through the extracellular region and enhances its signaling. Although this cis ‐interaction does not affect the PDGF ‐induced tyrosine phosphorylation of the receptor, the interaction of the cytoplasmic region of Necl‐5 with sprouty2 and the regulation of its activity are required for the enhancement of the PDGF receptor β signaling by Necl‐5. We investigated here the more detailed mechanism for this cis ‐interaction of Necl‐5 with the PDGF receptor β. Necl‐5 contains three Ig‐like domains and the PDGF receptor β contains five Ig‐like domains at their extracellular regions. We showed here that the third Ig‐like domain of Necl‐5 cis ‐interacted with the fifth Ig‐like domain of the PDGF receptor β. The recombinant protein of the third Ig‐like domain of Necl‐5 inhibited the cis ‐interaction of full‐length Necl‐5 with the PDGF receptor β and the PDGF ‐induced activation of the ERK signaling pathway that was enhanced by Necl‐5. These results revealed the novel roles of the third Ig‐like domain of Necl‐5 and the fifth Ig‐like domain of the PDGF receptor β in its signaling.