KMID : 0624620170500110584
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BMB Reports 2017 Volume.50 No. 11 p.584 ~ p.589
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Protein tyrosine phosphatase PTPN21 acts as a negative regulator of ICAM-1 by dephosphorylating IKK¥â in TNF-¥á-stimulated human keratinocytes
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Cho Young-Chang
Kim Ba-Reum Cho Sa-Yeon
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Abstract
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Intercellular adhesion molecule-1 (ICAM-1), which is induced by tumor necrosis factor (TNF)-¥á, contributes to the entry of immune cells into the site of inflammation in the skin. Here, we show that protein tyrosine phosphatase non-receptor type 21 (PTPN21) negatively regulates ICAM-1 expression in human keratinocytes. PTPN21 expression was transiently induced after stimulation with TNF-¥á. When overexpressed, PTPN21 inhibited the expression of ICAM-1 in HaCaT cells but PTPN21 C1108S, a phosphatase activity-inactive mutant, failed to inhibit ICAM-1 expression. Nuclear factor-¥êB (NF-¥êB), a key transcription factor of ICAM-1 gene expression, was inhibited by PTPN21, but not by PTPN21 C1108S. PTPN21 directly dephosphorylated phospho-inhibitor of ¥êB (I¥êB)-kinase ¥â (IKK¥â) at Ser177/181. This dephosphorylation led to the stabilization of I¥êB¥á and inhibition of NF-¥êB activity. Taken together, our results suggest that PTPN21 could be a valuable molecular target for regulation of inflammation in the skin by dephosphorylating p-IKK¥â and inhibiting NF-¥êB signaling.
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KEYWORD
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Inhibitor of ¥êB kinase, Intercellular adhesion molecule-1, Nuclear factor kappaB, Protein tyrosine phosphatase non-receptor type 21, Skin inflammation
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