https://scholars.lib.ntu.edu.tw/handle/123456789/550436
標題: | Spleen tyrosine kinase mediates EGFR signaling to regulate keratinocyte terminal differentiation | 作者: | Wu N.-L. Huang D.-Y. Wang L.-F. Kannagi R. Fan Y.-C. WAN-WAN LIN |
公開日期: | 2016 | 卷: | 136 | 期: | 1 | 起(迄)頁: | 192-201 | 來源出版物: | Journal of Investigative Dermatology | 摘要: | 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. ? 2015 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology. |
URI: | 2-s2.0-84959535810 https://scholars.lib.ntu.edu.tw/handle/123456789/550436 |
ISSN: | 0022202X | DOI: | 10.1038/JID.2015.381 | SDG/關鍵字: | cytokeratin 10; epidermal growth factor receptor; fostamatinib; gefitinib; involucrin; loricrin; protein kinase Syk; small interfering RNA; EGFR protein, human; epidermal growth factor receptor; protein kinase Syk; protein tyrosine kinase; signal peptide; Article; cell cycle S phase; cell differentiation; confocal microscopy; controlled study; gene expression; human; human cell; immunoprecipitation; in vitro study; keratinocyte; molecular interaction; priority journal; protein expression; protein function; protein localization; protein phosphorylation; protein protein interaction; psoriasis; real time polymerase chain reaction; signal transduction; cell culture; cell differentiation; cytology; flow cytometry; genetics; immunohistochemistry; keratinocyte; metabolism; needle biopsy; pathology; physiology; skin; Biopsy, Needle; Cell Differentiation; Cells, Cultured; Flow Cytometry; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Keratinocytes; Protein-Tyrosine Kinases; Real-Time Polymerase Chain Reaction; Receptor, Epidermal Growth Factor; RNA, Small Interfering; Signal Transduction; Skin |
顯示於: | 藥理學科所 |
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