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.
| Original language | English |
|---|---|
| Pages (from-to) | 4057-4062 |
| Number of pages | 6 |
| Journal | FEBS Letters |
| Volume | 584 |
| Issue number | 18 |
| DOIs | |
| State | Published - Sep 2010 |
| Externally published | Yes |
Keywords
- Cell proliferation
- EGFR
- GPR48
- HB-EGF
- Keratinocyte