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Stat5 phosphorylation is responsible for the excessive potency of HB‐EGF
Author(s) -
Heo Jeongyeon,
Kim Jae Geun,
Kim Sunghwan,
Kang Hara
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26639
Subject(s) - phosphorylation , stat5 , potency , chemistry , microbiology and biotechnology , pharmacology , biochemistry , biology , in vitro
Heparin‐binding EGF‐like growth factor (HB‐EGF) is a potent growth factor involved in wound healing and tumorigenesis. Despite the sequence similarity between HB‐EGF and EGF, HB‐EGF induces cellular proliferation and migration more potently than EGF. However, the differential regulation by HB‐EGF and EGF has not been thoroughly elucidated. In this study, we compared signaling pathways activated by HB‐EGF and EGF to understand the details of the molecular mechanism of the high potency induced by HB‐EGF. HB‐EGF specifically induced the phosphorylation of EGFR‐Y1045 and activated Stat5, which is responsible for promoting cell proliferation, and migration. The competition of phosphorylated EGFR‐Y1045 inhibited Stat5 activation and consequently lowered the effect of HB‐EGF on cell proliferation, suggesting that the phosphorylation of EGFR‐Y1045 is essential for the activation of Stat5. The phosphorylation of EGFR‐Y1045 and Stat5 induced by HB‐EGF was prevented by sequestering the heparin‐binding domain, suggesting that the heparin‐binding domain is critical for HB‐EGF‐mediated signaling and cellular responses. In conclusion, the heparin‐binding domain of HB‐EGF was responsible for EGFR‐mediated Stat5 activation, resulting in a more potent cellular proliferation, and migration than that mediated by EGF. This molecular mechanism is useful for understanding ligand‐specific EGFR signaling and developing biomedicines for wound healing or cancer therapy.