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GPR48‐Induced keratinocyte proliferation occurs through HB‐EGF mediated EGFR transactivation
Author(s) -
Wang Zhenlian,
Jin Chang,
Li Hongxia,
Li Canxia,
Hou Qiang,
Liu Mingyao,
Dong Xiang Da Eric,
Tu LiLi
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.08.028
Subject(s) - transactivation , keratinocyte , chemistry , microbiology and biotechnology , cancer research , biology , biochemistry , in vitro , gene expression , gene
GPR48 can mediate keratinocyte proliferation and migration. Our investigations showed that AG1478, an inhibitor of EGFR tyrosine kinase, could block GPR48‐mediated cellular processes. AG1478 treatment of Gpr48 +/+ cells also decreased phosphorylation of EGFR, ERK and STAT3. Subsequent screening using conditioned media immunodepleted of EGFR ligands identified HB‐EGF as the ligand responsible for phosphorylation of EGFR, ERK and STAT3. HB‐EGF was reduced in Gpr48 −/− cell culture medium, but its addition restored the phosphorylation of EGFR, ERK, STAT3, as well as cell proliferation. Confirmation that GPR48 mediates EGFR signaling pathway through HB‐EGF was subsequently performed using an inhibitor of HB‐EGF.