FEBS Letters · 2010 · 43 citations · 24 references
Life SciencesCell BiologyMolecular BiologyCell ProliferationCell SignalingSignal TransductionCancer Cell SignalingCell Proliferation ControlGrowth Factor SignalingMitogenic SignalingReceptor Tyrosine Kinase SignalingTyrosine Kinase InhibitorsCell Proliferation StimulationEgfr InhibitionEpidermal Growth Factor Receptor SignalingErk SignalingExtracellular Signal-regulated Kinase PathwayTyrosine Kinase InhibitionTyrosine Kinase Receptor SignalingTyrosine Kinase Receptors
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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