Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, United Kingdom; email:
Published: September 2019
AI Article Synopsis
Article Abstract
Bacteria depend on two-component systems to detect and respond to threats. Simple pathways comprise a single sensor kinase (SK) that detects a signal and activates a response regulator protein to mediate an appropriate output. These simple pathways with only a single SK are not well suited to making complex decisions where multiple different stimuli need to be evaluated. A recently emerging theme is the existence of multikinase networks (MKNs) where multiple SKs collaborate to detect and integrate numerous different signals to regulate a major lifestyle switch, e.g., between virulence, sporulation, biofilm formation, and cell division. In this review, the role of MKNs and the phosphosignaling mechanisms underpinning their signal integration and decision making are explored.
Center for Immunology and Hematology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address:
T helper 2 (Th2) cells play a dual role in the body by fighting parasites and aiding tissue repair, but they can also cause problems in conditions like asthma and tissue fibrosis.
Research showed that Th2 cells from asthma patients have increased levels of a protein called HIF2α, which is crucial for their pathogenic development.
Targeting HIF2α could be a potential treatment strategy for asthma, as its inhibition was found to reduce harmful Th2 cell differentiation and decrease airway inflammation.
MANAGING MEDULLARY THYROID CARCINOMA IN 2024: Medullary thyroid carcinoma is a rare neuroendocrine thyroid cancer with a heterogeneous prognosis which has the particularity of being associated with a RET gene mutation, germline in 20-25% of cases in the context of multiple endocrine neoplasia type 2 (NEM2), and somatic in 70% of sporadic cases. It is often diagnosed on a thyroid nodule or in the context of genetic screening. Calcitonin is a biological marker, used for diagnosis, monitoring of therapeutic response and prognostic evaluation.
UPMC Hillman Cancer Center, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Division of Regenerative Medicine, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92037, USA; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address:
Tumors reprogram their metabolism to generate complex neoplastic ecosystems. Here, we demonstrate that glioblastoma (GBM) stem cells (GSCs) display elevated activity of the malate-aspartate shuttle (MAS) and expression of malate dehydrogenase 2 (MDH2). Genetic and pharmacologic targeting of MDH2 attenuated GSC proliferation, self-renewal, and in vivo tumor growth, partially rescued by aspartate.
* Direct KRAS inhibitors are showing promise in clinical trials, but resistance to treatment is a concern, prompting the search for combination therapies.
* Unbiased drug screening identified effective combinations involving SOS1 inhibitors, PTPN11/SHP2 inhibitors, and multi-kinase inhibitors, validated using a unique KRAS-mutated patient-derived organoid model.
Centro de Investigaciones en Ciencias Microbiológicas, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, IC-11 Ciudad Universitaria Puebla, Apdo. Postal 1622, C. P. 72000, Puebla, Pue, Mexico.
The two-component system GacS/A and the posttranscriptional control system Rsm constitute a genetic regulation pathway in Gammaproteobacteria; in some species of Pseudomonas, this pathway is part of a multikinase network (MKN) that regulates the activity of the Rsm system. In this network, the activity of GacS is controlled by other kinases. One of the most studied MKNs is the MKN-GacS of Pseudomonas aeruginosa, where GacS is controlled by the kinases RetS and LadS; RetS decreases the kinase activity of GacS, whereas LadS stimulates the activity of the central kinase GacS.
