Open AccessZNT7 binds to CD 40 and influences CD 154‐triggered p38 MAPK activity in B lymphocytes—a possible regulatory mechanism for zinc in immune function
Author(s) -
Tepaamorndech Surapun,
Oort Pieter,
Kirschke Catherine P.,
Cai Yimeng,
Huang Liping
Publication year - 2017
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12211
Subject(s) - mapk/erk pathway , signal transduction , microbiology and biotechnology , phosphorylation , p38 mitogen activated protein kinases , immune system , protein kinase b , kinase , protein kinase a , biology , gene knockdown , chemistry , biochemistry , immunology , apoptosis
Zinc deficiency impairs the immune system leading to frequent infections. Although zinc is known to play critical roles in maintaining healthy immune function, the underlying molecular targets are largely unknown. In this study, we demonstrate that zinc is important for the CD 154– CD 40‐mediated activation of downstream signaling pathways in human B lymphocytes. CD 40 is a receptor localized on the cell surface of many immune cells, including B lymphocytes. It binds to CD 154, a membrane protein expressed on antigen‐activated T helper (Th) lymphocytes. This CD 154‐ CD 40 interaction leads to B‐cell activation. We showed that cellular zinc deficiency impaired the CD 154‐ CD 40‐mediated p38 mitogen‐activated protein kinase (p38 MAPK ) phosphorylation. We also showed that zinc supplemental treatment of B lymphocytes had limited effect on this CD 40‐mediated p38 MAPK signaling. Most importantly, we demonstrated that the zinc transporter protein zinc transporter 7 ( ZNT 7) interacted with CD 40 using immunoprecipitation analyses. ZNT 7 knockdown in B lymphocytes had a negative effect on the cell surface expression of CD 40. Consequently, the CD 40‐mediated p38 MAPK signaling transduction was down‐regulated in ZNT 7 KD B lymphocytes. Conversely, this p38 MAPK signaling activity was up‐regulated by overexpression (OE) of ZNT 7 in B lymphocytes. Moreover, we found that ZNT 7 knockdown in B lymphocytes constitutively up‐ and down‐regulated the inhibitor of i kappa B kinase and AKT serine/threonine kinase phosphorylation, respectively, which implies the activation of survival signaling in ZNT 7 KD B cells. We conclude that CD 40 is the target molecule for ZNT 7 in regulation of immune function of B lymphocytes.