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Pfnek-1, a NIMA-related kinase from the human malaria parasite Plasmodium falciparum: Biochemical properties and possible involvement in MAPK regulation

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KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification

Pierre Gönczy, Mathias Fournier

Lysine acetylation is a widespread post-translational modification regulating various biological processes. To characterize cellular functions of the human lysine acetyltransferases KAT2A (GCN5) and KAT2B (PCAF), we determined their acetylome by shotgun pr ...

2016

Unexpected Off-Targets and Paradoxical Pathway Activation by Kinase Inhibitors

Oliver Hantschel

Protein kinase inhibitors are an increasingly important class of targeted anticancer therapeutics. More than two dozen new drugs of this class have entered routine clinical use over the past decade. This review article focuses on how the development of met ...

2015

Kinase Regulation in Mycobacterium tuberculosis: Variations on a Theme

Oliver Hantschel, Sina Maren Reckel

In this issue of Structure, Lisa et al. (2015) examine how the PknG protein kinase of M. tuberculosis efficiently binds and phosphorylates substrates. The work highlights interesting parallels between PknG and eukaryotic protein kinases. ...

Elsevier2015

Parkinson disease mutant E46K enhances α-synuclein phosphorylation in mammalian cell lines, in yeast, and in vivo

Hilal Lashuel, Magdalena Zweckstetter, Abid Oueslati, Mohamed Bilal Fares, Martial Mbefo Kamdem

Although α-synuclein (α-syn) phosphorylation has been considered as a hallmark of sporadic and familial Parkinson disease (PD), little is known about the effect of PD-linked mutations on α-syn phosphorylation. In this study, we investigated the effects of ...

American Society for Biochemistry and Molecular Biology2015

Phosphorylation of the nuclear receptor corepressor 1 by protein kinase B switches its corepressor targets in the liver in mice

Johan Auwerx, Kristina Schoonjans, Dongryeol Ryu, Xu Wang, Adriano Maida

Nuclear receptor corepressor 1 (NCoR1) is a transcriptional coregulator that has wide-ranging effects on gene expression patterns. In the liver, NCoR1 represses lipid synthesis in the fasting state, whereas it inhibits activation of peroxisome proliferator ...

Wiley-Blackwell2015

Regulation of Plasmodium falciparum Development by Calcium-dependent Protein Kinase 7 (PfCDPK7)

Second messengers such as phosphoinositides and calcium are known to control diverse processes involved in the development of malaria parasites. However, the underlying molecular mechanisms and pathways need to be unraveled, which may be achieved by unders ...

Amer Soc Biochemistry Molecular Biology Inc2014

Cyclin-dependent kinase-like kinases (CLKs) are dual specificity protein kinases that phosphorylate Serine/Arginine-rich (SR) proteins involved in pre-mRNA processing. Four CLKs, termed PfCLK-1-4, can be identified in the human malaria parasite Plasmodium ...

Public Library Science2014

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The regulatory pathways required to maintain eukaryotic lipid homeostasis are largely unknown. We developed a systematic approach to uncover new players in the regulation of lipid homeostasis. Through an unbiased mass spectrometry-based lipidomic screening ...

Amer Soc Cell Biology2014

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The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both confo ...

2014

Acute systemic rapamycin induces neurobehavioral alterations in rats

Raphaël Doenlen

Rapamycin is a drug with antiproliferative and immunosuppressive properties, widely used for prevention of acute graft rejection and cancer therapy. It specifically inhibits the activity of the mammalian target of rapamycin (mTOR), a protein kinase known t ...

Elsevier Science Bv2014