Spleen tyrosine kinase mediates EGFR signaling to regulate keratinocyte terminal differentiation

Nan Lin Wu, Duen Yi Huang, Li Fang Wang, Reiji Kannagi, Yu Ching Fan, Wan Wan Lin

研究成果: 雜誌貢獻文章同行評審

21 引文 斯高帕斯(Scopus)


Spleen tyrosine kinase (Syk), a nonreceptor tyrosine kinase, was initially identified as a crucial regulator in proximal immunoreceptor signaling. Additional studies have revealed its pleiotropic roles, and drugs targeting Syk are under development for inflammatory diseases. Syk expression in the skin has been detected, but its functions in the skin are still unknown. Here, we found that Syk phosphorylation and expression in primary human keratinocytes decreased gradually along with terminal differentiation. Human skin specimens showed similar in vivo patterns. Syk inhibitors or knockdown of Syk increased the expression of differentiation markers under in vitro differentiation models. Furthermore, EGFR activation prominently induced Syk phosphorylation, which could be inhibited by the EGFR inhibitor gefitinib or knockdown of EGFR. The Src inhibitor also partially attenuated EGF-induced phosphorylation of Syk. However, Syk inhibition suppressed EGF-induced phosphorylation of EGFR. Immunoprecipitation and confocal microscopy further revealed the increased molecular interaction between EGFR and Syk after EGF stimulation. This study unravels the role of Syk in EGFR-mediated signaling and reveals regulatory roles of Syk in keratinocyte differentiation, suggesting the clinical potential of topical or systemic Syk inhibitors in the treatment of skin diseases with aberrant differentiation.
頁(從 - 到)192-201
期刊Journal of Investigative Dermatology
出版狀態已發佈 - 1月 1 2016

ASJC Scopus subject areas

  • 皮膚科
  • 生物化學
  • 細胞生物學
  • 分子生物學
  • 醫藥 (全部)


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