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Dendritic cell (DC) development begins in the bone marrow but is not completed until after immature progenitors reach their sites of residence in lymphoid organs. The hematopoietic growth factors regulating these processes are poorly understood. Here we examined the effects of signaling by the receptor tyrosine kinase Flt3 on macrophage DC progenitors in the bone marrow and on peripheral DCs. We found that the macrophage DC progenitor compartment was responsive to superphysiological amounts of Flt3 ligand but was not dependent on Flt3 for its homeostatic maintenance in vivo. In contrast, Flt3 was essential to the regulation of homeostatic DC development in the spleen, where it was needed to maintain normal numbers of DCs by controlling their division in the periphery.
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http://dx.doi.org/10.1038/ni.1615 | DOI Listing |
Inflammopharmacology
September 2025
Department of Pharmacology and Toxicology, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA University), Giza, Egypt.
The neuroprotective potential of tyrosine kinase inhibitors (TKIs), potent anticancer drugs, was verified against various neurodegenerative insults, but not Huntington's disease (HD). These promising outcomes were due to their ability to modulate various intracellular signalling pathways. Hence, the current study aimed to evaluate the neuroprotective effects of lapatinib and pazopanib in the 3-nitropropionic (3-NP)-induced HD model in rats.
View Article and Find Full Text PDFZhonghua Jie He He Hu Xi Za Zhi
September 2025
Department of nursing, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) are important treatments for EGFR mutant non-small cell lung cancer (NSCLC). However, the first and second generation EGFR-TKI face clinical limitations due to acquired resistance, such as the T790M mutation. Irreversible EGFR-TKI can significantly prolong the survival of patients by enhancing the inhibition of drug-resistant mutations through the covalent binding mechanism.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Cell Biol Lipids
September 2025
Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada; Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, V8W 2Y2, Canada; University of Victoria Genome BC Proteomics Centre, Vi
The class I phosphoinositide 3-kinase pathway (PI3K) is a master regulator of cellular growth, and plays essential roles in controlling immune cell function, metabolism, chemotaxis and proliferation. Activation of class I PI3Ks generates the signalling lipid PIP that activates multiple pro-growth signalling pathways. Class I PI3Ks can be activated by multiple plasma membrane stimuli, including G-protein coupled receptors, Ras superfamily GTPases, and receptor tyrosine kinases.
View Article and Find Full Text PDFMol Pharmacol
August 2025
Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Biomedical Research Center Seltersberg, Justus Liebig University of Giessen, Giessen, Germany. Electronic address:
The myristoylated preS1 domain (myr-preS1) of the hepatitis B virus (HBV) large surface protein is essential for binding to the receptor protein, Na/taurocholate co-transporting polypeptide (NTCP), and for the subsequent internalization of the virus-receptor complex. NTCP, which is expressed in hepatocytes, plays a physiological role in hepatic bile acid transport. Recent cryo-electron microscopy structures of the myr-preS1-NTCP complex were used to analyze virus-receptor interactions at the molecular level.
View Article and Find Full Text PDFBiochem Soc Trans
September 2025
Department of Biochemistry, McGill University, Montréal, QC, Canada.
The MET receptor tyrosine kinase is a pivotal regulator of cellular survival, motility, and proliferation. Mutations leading to skipping of exon 14 (METΔex14) within the juxtamembrane domain of MET impair receptor degradation and prolong oncogenic signaling, contributing significantly to tumor progression across multiple cancer types. METΔex14 mutations are associated with aggressive clinical behavior, therapeutic resistance, and poor outcomes.
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