GPR48-Induced keratinocyte proliferation occurs through HB-EGF mediated EGFR transactivation

Wang, Zhenlian; Jin, Chang; Li, Hongxia; Li, Canxia; Hou, Qiang; Liu, Mingyao; Dong, Xiang Da (Eric); Tu, LiLi

doi:10.1016/j.febslet.2010.08.028

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Volume 584, Issue 18 , Pages 4057-4062, 24 September 2010

GPR48-Induced keratinocyte proliferation occurs through HB-EGF mediated EGFR transactivation

Edited by Beat Imhof

Zhenlian Wang
- School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang 325003, China
- Key Laboratory of Vision Science, Ministry of Health of the People’s Republic of China, Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325003, China
- Both authors contributed equally to this study and shared first authorship.
Chang Jin
- School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang 325003, China
- Key Laboratory of Vision Science, Ministry of Health of the People’s Republic of China, Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325003, China
- Both authors contributed equally to this study and shared first authorship.
Hongxia Li
- School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang 325003, China
- Key Laboratory of Vision Science, Ministry of Health of the People’s Republic of China, Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325003, China
Canxia Li
- School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang 325003, China
- Key Laboratory of Vision Science, Ministry of Health of the People’s Republic of China, Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325003, China
Qiang Hou
- School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang 325003, China
- Key Laboratory of Vision Science, Ministry of Health of the People’s Republic of China, Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325003, China
Mingyao Liu
- Institute of Biosciences and Technology, and Department of Molecular and Cellular Medicine, Texas A& M University System Health Science Center, Houston, TX 77030, USA
Xiang Da (Eric) Dong
- Department of Surgery, Stamford Hospital - Affiliate of Columbia University, Stamford, CT 06904, USA
LiLi Tu
- School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang 325003, China
- Key Laboratory of Vision Science, Ministry of Health of the People’s Republic of China, Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325003, China
- Corresponding author at: School of Ophthalmology and Optometry, Wenzhou Medical College, 270 Xueyuan Road, Wenzhou, Zhejiang 325003, China. Fax: +011 86 577 88067934.

Received 14 July 2010; received in revised form 17 August 2010; accepted 17 August 2010. published online 23 August 2010.

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.

Keywords: GPR48, Keratinocyte, Cell proliferation, EGFR, HB-EGF