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Protein kinases are enzymes that attach phosphate to proteins, a process known as “phosphorylation”. Phosphorylation can change the shape of proteins and hence their ability to function, so that kinases are key controller enzymes that regulate almost every process in human cells. Many kinases have additional functions beyond phosphorylation, and some have even lost their ability to phosphorylate proteins altogether. These ‘inactive’ kinases are called ‘pseudokinases’, from the Greek word ‘pseudos’ (Engl. ‘false’). Pseudokinases often evolved unique ways to relay messages in the cell and to impact cellular processes. …more

Missense mutations that hyperactivate the LRRK2 protein kinase are a common cause of familial Parkinson’s disease. Recruitment of LRRK2 to membranes leads to its activation, where it phosphorylates a group of Rab GTPase proteins, including Rab10 and Rab12, within the effector-binding switch-II motif.

 

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Research by Kris Clark, a former postdoc in Philip Cohen's lab, led to the discovery eight years ago that the SIK subfamily of protein kinases suppress the production of the anti-inflammatory cytokine IL-10 by phosphorylating and inactivating CRTC3, co-activator of the transcription factor CREB.  Excitingly, pharmacological inhibition of the SIKs greatly enhanced the production of IL-10, and transformed macrophages from an inflammatory M1 state to an anti-inflammatory M2b state that is thought to be important for the resolution of inflammation and the repair of tissue damage. …more

Autophagy is a key cellular process that degrades unwanted, damaged or toxic cellular intracellular components and its dysfunction has been linked to many diseases ranging from cancer to neurodegeneration. The kinase ULK1 is critical in initiating autophagy and is thus an attractive therapeutic target, yet we do not fully understand how ULK1 controls autophagy induction. Using ULK1 inhibitors developed by the Ganley Lab and others, former PhD student Maria Zachari and current student Marianna Longo were able to show that ULK1 inhibition blocks autophagy but in an unexpected way. …more

Latest research from Greg Findlay’s lab in the MRC Protein Phosphorylation and Ubiquitylation Unit (MRC PPU) is published today in Developmental Cell. The work discovered a new pathway which is disrupted in people with Intellectual Disability and could provide a new therapeutic strategy for these individuals.

 

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MRC PPU Postdoc Dr Adam Fletcher has been awarded a Future Leaders Fellowship by UKRI, to begin his independent research programme at the MRC-University of Glasgow Centre for Virus Research (CVR) at the University of Glasgow.

 

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Dario Alessi and Miratul Muqit together with Stanford University researchers Suzanne Pfeffer and Monther Abu-Remaileh have been awarded a prestigious grant from the Aligning Science Across Parkinson’s (ASAP) initiative to further understanding of how LRRK2 is linked to Parkinson’s disease. …more

Tricia Cohen, co-founding Principal Investigator of the MRC Protein Phosphorylation Unit died from Lymphoma on August 2020. She was 76. …more

While SLS summer school students in the MRC Protein Phosphorylation Unit usually expect to gain wet lab experience and benefit from working alongside PhD students and postdoctoral researchers on the bench, the COVID-19 pandemic has had a major impact on this year’s programme as access to the labs was restricted and placements cancelled. However, some students have completed remote projects, including Neringa Pratuseviciute, a 4th Year BSc(Hons) Neuroscience student from the University of Dundee. Before the COVID-19 lockdown restrictions came into place, Neringa had been looking forward to her summer placement in Esther Sammler’s lab. …more

In this new paper, published in eLife, a team of researchers led by Dr. Tom Deegan in Karim Labib’s lab have recapitulated the ubiquitylation and disassembly of the eukaryotic replisome in a test tube using over 50 purified proteins. Every time a cell divides, it must make a complete, new copy of every one of its 46 chromosomes, each of which consists of a single DNA molecule that contains an individual’s genetic blueprint. …more