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  • Title: GPR48-Induced keratinocyte proliferation occurs through HB-EGF mediated EGFR transactivation.
    Author: Wang Z, Jin C, Li H, Li C, Hou Q, Liu M, Dong Xda E, Tu L.
    Journal: FEBS Lett; 2010 Sep 24; 584(18):4057-62. PubMed ID: 20732323.
    Abstract:
    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.
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