Spleen Tyrosine Kinase Mediates EGFR Signaling to Regulate Keratinocyte Terminal Differentiation

The Journal of Investigative Dermatology
Nan-Lin WuWan-Wan Lin

Abstract

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 keratinoc...Continue Reading

Citations

Jan 24, 2019·Expert Opinion on Biological Therapy·Randall LiEmma Guttman-Yassky
Jul 19, 2019·Immunological Medicine·Hiraku Suga, Shinichi Sato
Apr 15, 2017·Oncotarget·Barbara HeidenreichRajiv Kumar
Dec 12, 2018·American Journal of Clinical Dermatology·Helen He, Emma Guttman-Yassky
Aug 1, 2019·Paediatric Drugs·Henry L NguyenMegha M Tollefson
Feb 12, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ling-Ya ChiuWan-Wan Lin

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