Rapid and transient palmitoylation of the tyrosine kinase Lck mediates Fas signaling

Proceedings of the National Academy of Sciences of the United States of America
Askar M Akimzhanov, Darren Boehning

Abstract

Palmitoylation is the posttranslational modification of proteins with a 16-carbon fatty acid chain through a labile thioester bond. The reversibility of protein palmitoylation and its profound effect on protein function suggest that this modification could play an important role as an intracellular signaling mechanism. Evidence that palmitoylation of proteins occurs with the kinetics required for signal transduction is not clear, however. Here we show that engagement of the Fas receptor by its ligand leads to an extremely rapid and transient increase in palmitoylation levels of the tyrosine kinase Lck. Lck palmitoylation kinetics are consistent with the activation of downstream signaling proteins, such as Zap70 and PLC-γ1. Inhibiting Lck palmitoylation not only disrupts proximal Fas signaling events, but also renders cells resistant to Fas-mediated apoptosis. Knockdown of the palmitoyl acyl transferase DHHC21 eliminates activation of Lck and downstream signaling after Fas receptor stimulation. Our findings demonstrate highly dynamic Lck palmitoylation kinetics that are essential for signaling downstream of the Fas receptor.

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Citations

Jan 1, 2016·Proceedings of the National Academy of Sciences of the United States of America·Sabrina M HollandGareth M Thomas
Jun 1, 2016·Molecular Membrane Biology·Audrey Montersino, Gareth M Thomas
Feb 24, 2017·Molecular Biology of the Cell·Kinga Borzęcka-SolarzKatarzyna Kwiatkowska
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Feb 7, 2018·Frontiers in Immunology·Justyna SobocińskaKatarzyna Kwiatkowska
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Jun 24, 2020·Proceedings of the National Academy of Sciences of the United States of America·Qianru WeiNicholas R J Gascoigne
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Jan 29, 2021·The FEBS Journal·Hening Lin
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May 29, 2021·Scientific Reports·Xiaoyuan YangSarah Y Yuan
Jun 4, 2021·Journal of Cell Science·Shayahati BieerkehazhiAskar M Akimzhanov
Jun 23, 2021·Journal of Cell Science·Savannah J WestAskar M Akimzhanov
Oct 3, 2019·Accounts of Chemical Research·Saara-Anne AziziBryan C Dickinson
Oct 6, 2021·Open Biology·Yasmin A KadryEric S Witze

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