Protein tyrosine phosphatase PTPN21 acts as a negative regulator of ICAM-1 by dephosphorylating IKK beta in TNF-alpha-stimulated human keratinocytes

초록

Intercellular adhesion molecule-1 (ICAM-1), which is induced by tumor necrosis factor (TNF)-alpha, 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-alpha. 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-kappa B (NF-kappa B), a key transcription factor of ICAM-1 gene expression, was inhibited by PTPN21, but not by PTPN21 C1108S. PTPN21 directly dephosphorylated phospho-inhibitor of kappa B (I kappa B)-kinase. (IKK beta) at Ser177/181. This dephosphorylation led to the stabilization of I kappa B alpha and inhibition of NF-kappa B 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 beta and inhibiting NF-kappa B signaling.

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