Acetylation regulates the MKK4-JNK pathway in T cell receptor signaling.

Abstract:

:T cell functions are regulated by multiple signaling cascades, including the MKK4-JNK (c-Jun NH2 terminal kinase) pathway. However, the mechanism regulating the MKK4-JNK axis in T cells remains unclear. Herein, we demonstrated that protein acetylation modulates JNK activity induced by T cell receptor (TCR) activation. The acetyltransferase, CREB-binding protein (CBP), is transported from the nucleus to the cytoplasm in response to TCR cross-linking. To investigate the role of CBP in TCR signaling, we overexpressed CBP in the cytoplasm of Jurkat cells, a human T lymphocyte line. Enforced expression of cytoplasmic CBP led to MKK4 acetylation and interfered with MKK4-mediated JNK phosphorylation. Insufficient JNK activity decreased the activity of the transcription factor, AP-1. In contrast, other transcription factors, NF-κB and NFAT, stimulated with anti-CD3 and anti-CD28 antibodies were activated normally in the presence of cytoplasmic-CBP. These results provide valuable insights into the role of acetylation in MKK4-JNK signaling in T cells.

journal_name

Immunol Lett

journal_title

Immunology letters

authors

Matsui Y,Kuwabara T,Eguchi T,Nakajima K,Kondo M

doi

10.1016/j.imlet.2017.12.002

subject

Has Abstract

pub_date

2018-02-01 00:00:00

pages

21-28

eissn

0165-2478

issn

1879-0542

pii

S0165-2478(17)30410-8

journal_volume

194

pub_type

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