A key event for Ras transformation involves the direct physical association between Ras and the Raf-1 kinase. This interaction promotes both Raf translocation to the plasma membrane and activation of Raf kinase activity. Although substantial experimental evidence has demonstrated that Raf residues 51-131 alone are sufficient for Ras binding, conflicting observations have suggested that the Raf cysteine-rich domain (residues 139-184) may also be important for interaction with Ras. To clarify the role of the Raf cysteine-rich domain in Ras-Raf binding, we have compared the ability of two distinct Raf fragments to interact with Ras using both in vitro Ras binding and in vivo Ras inhibition assays. First, we determined that both Raf sequences 2-140 and 139-186 (designated Raf-Cys) showed preferential binding to active, GTP-bound Ras in vitro. Second, we observed that Raf-Cys antagonized oncogenic Ras(Q61L)-mediated transactivation of Ras-responsive elements and focus-forming activity in NIH 3T3 cells and insulin-induced germinal vesicle breakdown in Xenopus laevis oocytes in vivo. This inhibitory activity suggests that Raf-Cys can interact with Ras in vivo. Taken together, these results suggest that Ras interaction with two distinct domains of Raf-1 may be important in Ras-mediated activation of Raf kinase activity.
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http://dx.doi.org/10.1074/jbc.270.17.9809 | DOI Listing |
J Diabetes
January 2025
Joslin Diabetes Center, Affiliated With Harvard Medical School, Boston, Massachusetts, USA.
Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are established treatment options for type 2 diabetes (T2D). In addition to their glycemic benefit, GLP-1 RAs also induce weight loss by suppressing appetite via hypothalamic pathways. However, it remains unclear whether weight reduction is the primary driver of glycemic improvement.
View Article and Find Full Text PDFJ ECT
January 2025
From the Department of Psychiatry, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
Objectives: This study investigates repeated oral esketamine as a substitution strategy for maintenance electroconvulsive therapy (M-ECT) in eight patients with treatment-resistant depression (TRD).
Methods: In a 6-week dosing phase, esketamine was titrated from 0.5 or 1.
Toxins (Basel)
January 2025
Faculty of Sciences, University of Balamand, Al-Kourah, P.O. Box 100, Tripoli 1300, Lebanon.
Hyperalgesia is a condition marked by an abnormal increase in pain sensitivity, often occurring in response to tissue injury, inflammation, or prolonged exposure to certain medications. Inflammatory mediators, such as cytokines IL-1β, IL-6, and TNF-α, play a central role in this process, amplifying pain perception. Developing effective treatments that address the underlying mechanisms of hyperalgesia is an active field of research.
View Article and Find Full Text PDFVaccines (Basel)
January 2025
Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitides, Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of RAS (Institute of Poliomyelitis), Moscow 108819, Russia.
: We evaluate the immunotherapeutic potential of the yellow fever virus vaccine strain 17D (YFV 17D) for intratumoral therapy of pancreatic cancer in mice. : The cytopathic effect of YFV 17D on mouse syngeneic pancreatic cancers cells were studied both in vitro and in vivo and on human pancreatic cancers cells in vitro. : YFV 17D demonstrated a strong cytopathic effect against human cancer cells in vitro.
View Article and Find Full Text PDFJ Fungi (Basel)
January 2025
Joint Vietnam-Russia Tropical Science and Technology Research Center, Nguyen Van Huyen, Nghia Do, Cau Giay, Hanoi 122100, Vietnam.
The diversity and resource potential of macroscopic fungi in tropical regions remain understudied. Vietnam, being in a biodiversity hotspot, has a large number of new fungal species that are of interest for biotechnology and medicine. The presence of a large number of protected areas in Vietnam creates favorable opportunities for the study and ex situ conservation of tropical biodiversity.
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