Regulation of T cell receptor signaling by protein acyltransferase DHHC21
- PDF / 820,918 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 5 Downloads / 217 Views
SHORT COMMUNICATION
Regulation of T cell receptor signaling by protein acyltransferase DHHC21 Ying Fan1,2 · Bieerkehazhi Shayahati1 · Ritika Tewari1 · Darren Boehning2 · Askar M. Akimzhanov1 Received: 22 April 2020 / Accepted: 26 July 2020 © Springer Nature B.V. 2020
Abstract S-acylation reversible—post-translational lipidation of cysteine residues—is emerging as an important regulatory mechanism in T cell signaling. Dynamic S-acylation is critical for protein recruitment into the T cell receptor complex and initiation of the subsequent signaling cascade. However, the enzymatic control of protein S-acylation in T cells remains poorly understood. Here, we report a previously uncharacterized role of DHHC21, a member of the mammalian family of DHHC protein acyltransferases, in regulation of the T cell receptor pathway. We found that loss of DHHC21 prevented S-acylation of key T cell signaling proteins, resulting in disruption of the early signaling events and suppressed expression of T cell activation markers. Furthermore, downregulation of DHHC21 prevented activation and differentiation of naïve T cells into effector subtypes. Together, our study provides the first direct evidence that DHHC protein acyltransferases can play an essential role in regulation of T cell-mediated immunity. Keywords T-cell · T helper cells · DHHC21 · Acyltransferase · Protein acylation · Protein palmitoylation · Cell signaling · Signal transduction Abbreviations TCR T cell receptor LAT Linker for activation of T cells PAT Protein acyltransferase Th T helper Cell activation is a complex process critical for proliferation, regulation, and proper acquisition of T cell effector function. It is initiated upon ligation of the T cell receptor (TCR) by the peptide/major histocompatibility complex presented by the antigen-presenting cell. Engagement of the TCR triggers a cascade Ying Fan and Bieerkehazhi Shayahati contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05691-1) contains supplementary material, which is available to authorized users. * Askar M. Akimzhanov [email protected] 1
Department of Biochemistry and Molecular Biology, University of Texas-McGovern Medical School, 6431 Fannin Street, Suite 6.200, Houston, TX 77030, USA
Present Address: Cooper Medical School of Rowan University, 401 Broadway, Camden, NJ 08103, USA
2
of signaling events that ultimately results in specific functional outcomes modulated by co-stimulatory molecules and cytokines [1, 2]. The Src family tyrosine kinase Lck is among the first signaling molecules activated in response to TCR stimulation. Lck is rapidly recruited to the TCR where it phosphorylates TCRassociated CD3 and ζ-chain immunoreceptor tyrosine-based activation motifs [2, 3]. Phosphorylation of these motifs creates a docking site for another regulatory kinase, ZAP70, resulting in its binding to the TCR and subsequent activation. Activated ZAP70 proceeds to phosphorylate its substrate
Data Loading...
