To perceive pathogens, plants employ pattern recognition receptor (PRR) complexes, which then transmit these signals via the receptor-like cytoplasmic kinase BIK1 to induce defense responses. How BIK1 activity and stability are controlled is still not completely understood. Here, we show that the Hippo/STE20 homolog MAP4K4 regulates BIK1-mediated immune responses. MAP4K4 associates and phosphorylates BIK1 at Ser233, Ser236, and Thr242 to ensure BIK1 stability and activity. Furthermore, MAP4K4 phosphorylates PP2C38 at Ser77 to enable flg22-induced BIK1 activation. Our results uncover that a Hippo/STE20 homolog, MAP4K4, maintains the homeostasis of the central immune component BIK1.
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http://dx.doi.org/10.15252/embr.201947965 | DOI Listing |
Sci Rep
January 2025
Children's Research Center, Division of Oncology, University Children's Hospital Zürich, Zürich, Switzerland.
De-regulated protein expression contributes to tumor growth and progression in medulloblastoma (MB), the most common malignant brain tumor in children. MB is associated with impaired differentiation of specific neural progenitors, suggesting that the deregulation of proteins involved in neural physiology could contribute to the transformed phenotype in MB. Calsynthenin 1 (CLSTN1) is a neuronal protein involved in cell-cell interaction, vesicle trafficking, and synaptic signaling.
View Article and Find Full Text PDFmedRxiv
December 2024
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Recent advancements in Parkinson's disease (PD) drug development have been significantly driven by genetic research. Importantly, drugs supported by genetic evidence are more likely to be approved. While genome-wide association studies (GWAS) are a powerful tool to nominate genomic regions associated with certain traits or diseases, pinpointing the causal biologically relevant gene is often challenging.
View Article and Find Full Text PDFCNS Neurosci Ther
November 2024
Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Aims: Existing observational studies examining the effect of body fat on the risk of Parkinson disease (PD) have yielded inconsistent results. We aimed to investigate this causal relationship at the genetic level.
Methods: We employed two-sample Mendelian randomization (TSMR) to investigate the causal effects of body fat on PD, with multiple sex-specific body fat measures being involved.
Brain Res
January 2025
Molecular Biology Research Lab, Department of Zoology, Deshbandhu College, University of Delhi, Kalkaji, New Delhi 110019, India; Delhi School of Public Health, Institute of Eminence, University of Delhi, Delhi 110007, India. Electronic address:
Glaucoma, a prevalent eye ailment causing irreversible vision loss, affects over 295 million individuals globally, necessitating the exploration of novel therapeutic avenues. Despite extensive research on targets like the phosphodiesterase enzyme and rho kinase, the potential of MAP4K4 in glaucoma remains untapped. This study aims to identify potent MAP4K4 inhibitors to counteract retinal cell apoptosis and oxidative stress associated with glaucoma.
View Article and Find Full Text PDFJ Lipid Res
November 2024
Department of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address:
Metabolic dysfunction-associated steatotic liver disease has emerged as a leading global cause of chronic liver disease. Our recent translational investigations have shown that the STE20-type kinases comprising the GCKIII subfamily-MST3, STK25, and MST4-associate with hepatic lipid droplets and regulate ectopic fat storage in the liver; however, the mode of action of these proteins remains to be resolved. By comparing different combinations of the silencing of MST3, STK25, and/or MST4 in immortalized human hepatocytes, we found that their single knockdown results in a similar reduction in hepatocellular lipid content and metabolic stress, without any additive or synergistic effects observed when all three kinases are simultaneously depleted.
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