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

ABSTRACT: Intercellular adhesion molecule-1 (ICAM-1), which is induced by tumor necrosis factor (TNF)-?, 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-?. 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-?B (NF-?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 ?B (I?B)-kinase ? (IKK?) at Ser177/181. This dephosphorylation led to the stabilization of I?B? and inhibition of NF-?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? and inhibiting NF-?B signaling. [BMB Reports 2017; 50(11): 584-589].

SUBMITTER: Cho YC 

PROVIDER: S-EPMC5720473 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature