Palmitoylation-dependent control of JAK1 kinase signaling governs responses to neuropoietic cytokines and survival in DRG neurons

Hernandez, Luiselys M.; Montersino, Audrey; Niu, Jingwen; Guo, Shuchi; Faezov, Bulat; Sanders, Shaun S.; Dunbrack, Roland L.; Thomas, Gareth M.

doi:10.1016/j.jbc.2023.104965

Cited by 8 publications

(2 citation statements)

References 52 publications

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“…3B). Jak1 is S- palmitoylated at two cysteine residues (46) and we assured that the level of S- palmitoylated endogenous Jak1 eluted from streptavidin beads or the total amount of the protein in input lysates were not affected by the overproduction of zDHHC7 or zDHHC17 (Supplemental Fig. S3C, D).…”

Section: Resultsmentioning

confidence: 99%

Diacylglycerol kinase-ε isS-palmitoylated on cysteine in the cytoplasmic end of its N-terminal transmembrane fragment

Traczyk

Hromada-Judycka

Swiatkowska

et al. 2023

Preprint

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Diacylglycerol kinase-epsilon (DGKepsilon) catalyzes phosphorylation of diacylglycerol to phosphatidic acid with a unique specificity toward 1-stearoyl-2-arachidonoyl-sn-glycerol which is a backbone of phosphatidylinositol (PI).DGKepsilon plays a crucial role in the PI cycle thereby maintaining the cellular level of phosphorylated PI derivatives of signaling activity, and in lipid metabolism. DGKepsilon dysfunction is linked with the development of atypical hemolytic uremic syndrome (aHUS) and other diseases in humans. Despite the DGKepsilon significance, data on the regulation of its functioning by possible co/post-translational modifications are scarce. Here we report that DGKepsilon is S-palmitoylated at Cys38/40 (mouse/human DGKepsilon) located at the cytoplasmic end of its N-terminal putative transmembrane fragment. The S-palmitoylation of DGKepsilon was revealed by metabolic labeling of cells with a palmitic acid analogue followed by click chemistry, and with acyl-biotin and acyl-PEG exchange assays. The zDHHC7, 17 and 6/16 S-acyltransferases were found to catalyze DGKepsilon S-palmitoylation which also increased the DGKepsilon abundance, likely by affecting its stability. Given the localization of the majority of DGKepsilon and zDHHC6 in the endoplasmic reticulum and zDHHC7 and zDHHC17 in the Golgi apparatus, trafficking of a fraction of DGKepsilon through the Golgi apparatus toward the plasma membrane is plausible. The Cys38Ala substitution moderately upregulated the activity of DGKepsilon, suggesting an inhibitory effect of the acylation in wild type DGKepsilon. In contrast to Cys38Ala, the substitution of neighboring Pro31 with Ala diminished the amount and the activity of DGKepsilon. Taken together, our data indicate that S-palmitoylation can fine-tune DGKepsilon activity and affect its abundance and cellular localization.

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Section: Resultsmentioning

confidence: 99%

Diacylglycerol kinase-ε isS-palmitoylated on cysteine in the cytoplasmic end of its N-terminal transmembrane fragment

Traczyk

Hromada-Judycka

Swiatkowska

et al. 2023

Preprint

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“…Among zDHHCs, zDHHC3 is stably localized in the Golgi apparatus ( Niki et al, 2023 ). JAK1 palmitoylation is important for neuronal cell medium-dependent signaling and neuronal survival, and zDHHC3 or zDHHC7 can bind to palmitoylated JAK1 ( Hernandez et al, 2023 ). zDHHC7 affects anxiety-related behaviors only in females, a finding that may be used to understand the differences in hormone receptors, neuronal morphology, synaptic plasticity, and molecular signaling pathways between males and females ( Kerkenberg et al, 2021a ).…”

Section: Role Of Zdhhcs In Neurobiologymentioning

confidence: 99%

The role of s-palmitoylation in neurological diseases: implication for zDHHC family

Liao,

Huang,

Liu

et al. 2024

Front. Pharmacol.

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S-palmitoylation is a reversible posttranslational modification, and the palmitoylation reaction in human-derived cells is mediated by the zDHHC family, which is composed of S-acyltransferase enzymes that possess the DHHC (Asp-His-His-Cys) structural domain. zDHHC proteins form an autoacylation intermediate, which then attaches the fatty acid to cysteine a residue in the target protein. zDHHC proteins sublocalize in different neuronal structures and exert dif-ferential effects on neurons. In humans, many zDHHC proteins are closely related to human neu-rological disor-ders. This review focuses on a variety of neurological disorders, such as AD (Alz-heimer’s disease), HD (Huntington’s disease), SCZ (schizophrenia), XLID (X-linked intellectual disability), attention deficit hyperactivity disorder and glioma. In this paper, we will discuss and summarize the research progress regarding the role of zDHHC proteins in these neu-rological disorders.

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Redox, cysteines, and kinases—A triad sustaining myeloid leukemia

Marensi

2024

Advances in Cancer Research

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Palmitoylation-dependent control of JAK1 kinase signaling governs responses to neuropoietic cytokines and survival in DRG neurons

Cited by 8 publications

References 52 publications

Diacylglycerol kinase-ε isS-palmitoylated on cysteine in the cytoplasmic end of its N-terminal transmembrane fragment

Diacylglycerol kinase-ε isS-palmitoylated on cysteine in the cytoplasmic end of its N-terminal transmembrane fragment

The role of s-palmitoylation in neurological diseases: implication for zDHHC family

Redox, cysteines, and kinases—A triad sustaining myeloid leukemia

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