The secretory pathway kinases

Sreelatha, Anju; Kinch, Lisa N.; Tagliabracci, Vincent S.

doi:10.1016/j.bbapap.2015.03.015

Cited by 33 publications

(40 citation statements)

References 84 publications

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“…These enzymes share limited sequence similarity with canonical protein kinases, and some of them phosphorylate proteins, whereas others phosphorylate proteoglycan substrates (7)(8)(9). One member, family with sequence similarity 20C (Fam20C), is the physiological Golgi casein kinase (5,10).…”

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confidence: 99%

Phosphorylation of spore coat proteins by a family of atypical protein kinases

Nguyen

Sreelatha

Durrant

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The modification of proteins by phosphorylation occurs in all life forms and is catalyzed by a large superfamily of enzymes known as protein kinases. We recently discovered a family of secretory pathway kinases that phosphorylate extracellular proteins. One member, family with sequence similarity 20C (Fam20C), is the physiological Golgi casein kinase. While examining distantly related protein sequences, we observed low levels of identity between the spore coat protein H (CotH), and the Fam20C-related secretory pathway kinases. CotH is a component of the spore in many bacterial and eukaryotic species, and is required for efficient germination of spores in Bacillus subtilis; however, the mechanism by which CotH affects germination is unclear. Here, we show that CotH is a protein kinase. The crystal structure of CotH reveals an atypical protein kinase-like fold with a unique mode of ATP binding. Examination of the genes neighboring cotH in B. subtilis led us to identify two spore coat proteins, CotB and CotG, as CotH substrates. Furthermore, we show that CotH-dependent phosphorylation of CotB and CotG is required for the efficient germination of B. subtilis spores. Collectively, our results define a family of atypical protein kinases and reveal an unexpected role for protein phosphorylation in spore biology.

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confidence: 99%

Phosphorylation of spore coat proteins by a family of atypical protein kinases

Nguyen

Sreelatha

Durrant

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…As the function of Fjx1 is still obscure, we cannot exclude that, besides the canonical targets Ft and Ds, additional direct targets of Fjx1 exist. This is because Fjx1 is a Golgi secretory pathway kinase and therefore likely involved in many biological processes, as already shown for its closely related homolog Fam20C . Additionally, Fjx1 protein undergoes partial proteolytic cleavage at the N‐terminus, with the secretion of the resultant fragment that can function as signalling ligand, influencing surrounding cells.…”

Section: Discussionmentioning

confidence: 85%

Four‐jointed knock‐out delays renal failure in an ADPKD model with kidney injury

Formica

Happe

Veraar

et al. 2019

The Journal of Pathology

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Autosomal Dominant Polycystic Kidney Disease is characterised by the development of fluid‐filled cysts in the kidneys which lead to end‐stage renal disease (ESRD). In the majority of cases, the disease is caused by a mutation in the Pkd1 gene. In a previous study, we demonstrated that renal injury can accelerate cyst formation in Pkd1 knock‐out (KO) mice. In that study, we found that after injury four‐jointed (Fjx1), an upstream regulator of planar cell polarity and the Hippo pathway, was aberrantly expressed in Pkd1 KO mice compared to WT. Therefore, we hypothesised a role for Fjx1 in injury/repair and cyst formation. We generated single and double deletion mice for Pkd1 and Fjx1, and we induced toxic renal injury using the nephrotoxic compound 1,2‐dichlorovinyl‐cysteine. We confirmed that nephrotoxic injury can accelerate cyst formation in Pkd1 mutant mice. This caused Pkd1 KO mice to reach ESRD significantly faster; unexpectedly, double KO mice survived significantly longer. Cyst formation was comparable in both models, but we found significantly less fibrosis and macrophage infiltration in double KO mice. Taken together, these data suggest that Fjx1 disruption protects the cystic kidneys against kidney failure by reducing inflammation and fibrosis. Moreover, we describe, for the first time, an interesting (yet unidentified) mechanism that partially discriminates cyst growth from fibrogenesis. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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“…Protein kinases are involved in several cellular mechanisms, and, when activated, trigger pathways and processes of great biological importance . Physiologically, kinases catalyse the phosphorylation of proteins regulating essential intracellular and extracellular processes as post‐translational, structural and functional modifications of cellular proteins . In addition, kinases are involved in growth and cell death mechanisms influencing the development of various chronic diseases such as cancer .…”

Section: Introductionmentioning

confidence: 99%

Myricetin inhibits panel of kinases implicated in tumorigenesis

Stoll

Bitencourt

Laufer

et al. 2019

Basic Clin Pharma Tox

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Myricetin is a flavonoid with several biological properties, including antioxidant and anti‐inflammatory features. Its protective effect in chronic diseases may occur through the inhibition of protein kinases that trigger inflammation and carcinogenesis pathways. Considering the influence of kinases on such pathological disorders, it is crucial to study compounds that inhibit these proteins. This study aims to evaluate the inhibitory potential of 14 flavonoids on TNF‐α release in human whole blood as well as the inhibitory potential of myricetin towards kinases involved in tumorigenesis. Our results showed that, out of all flavonoids, myricetin had the highest inhibitory effect on TNF‐α level. In addition, myricetin showed potential as a multi‐anti‐kinase compound, reducing the activity of 7 kinases by >70% and of 9 kinases by >90%. Together these data demonstrate the great inhibitory activity of myricetin on tumorigenic kinases and potential for the development of new therapeutics.

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The secretory pathway kinases

Cited by 33 publications

References 84 publications

Phosphorylation of spore coat proteins by a family of atypical protein kinases

Phosphorylation of spore coat proteins by a family of atypical protein kinases

Four‐jointed knock‐out delays renal failure in an ADPKD model with kidney injury

Myricetin inhibits panel of kinases implicated in tumorigenesis

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