The Ras/Raf/MEK/ERK cascade is a highly conserved signal transduction module, whose activation results in a number of different physiological outcomes. Depending on the cell type or the stimulus used, the pathway has been implicated in proliferation, differentiation, apoptosis, and migration. Because of this wide range of activities, these kinases are considered attractive (anticancer) therapeutic targets. However, their essential functions in the context of the whole organism are still incompletely known. Here, we describe immunohistochemical and immunofluorescence methods that can be used to define the essential function(s) and the relevant downstream targets of Raf-1, B-Raf, and Mek-1 in in vivo models of organ development, remodeling, and neoplasia.
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http://dx.doi.org/10.1007/978-1-60761-795-2_26 | DOI Listing |
Genes (Basel)
September 2024
School of Chemical, Biological, and Materials Engineering and Sciences, Mapúa University, Manila City 1002, Philippines.
Biochem Biophys Res Commun
November 2024
Mediterranean Institute for Life Sciences, Split, Croatia; Donnelly Centre, University of Toronto, Temerty School of Medicine, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Ontario, Canada; Department of Biochemistry, University of Toronto, Ontario, Canada; School of Medicine, University of Split, Croatia. Electronic address:
Protein-protein interactions (PPIs) play crucial roles in cellular signaling, transmitting signals from the cell surface to its interior. One of the most important signaling cascades is the RAS-RAF-MEK-ERK pathway. This pathway is initiated by various upstream signaling reactions, including receptor tyrosine kinase (RTK) activation, and it controls many biological functions like cell proliferation, differentiation, and survival.
View Article and Find Full Text PDFSci Rep
August 2024
Key Laboratory for Translational Research and Innovative Therapeutics of Gastrointestinal Oncology, Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hepatocellular carcinoma (HCC) still presents poor prognosis with low overall survival rates and limited therapeutic options available. Recently, attention has been drawn to peptidomic analysis, an emerging field of proteomics for the exploration of new potential peptide drugs for the treatment of various diseases. However, research on the potential function of HCC peptides is lacking.
View Article and Find Full Text PDFFront Cardiovasc Med
July 2024
Bristol Heart Institute, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Cardiovascular disease (CVD) represents the leading cause of mortality and disability all over the world. Identifying new targeted therapeutic approaches has become a priority of biomedical research to improve patient outcomes and quality of life. The RAS-RAF-MEK (mitogen-activated protein kinase kinase)-ERK (extracellular signal-regulated kinase) pathway is gaining growing interest as a potential signaling cascade implicated in the pathogenesis of CVD.
View Article and Find Full Text PDFJ Med Chem
April 2024
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu 610041, China.
The RAS-RAF-MEK-ERK signaling cascade is abnormally activated in various tumors, playing a crucial role in mediating tumor progression. As the key component at the terminal stage of this cascade, ERK1/2 emerges as a potential antitumor target and offers a promising therapeutic strategy for tumors harboring BRAF or RAS mutations. Here, we identified with a (thiophen-3-yl)aminopyrimidine scaffold as a potent ERK1/2 inhibitor through structure-guided optimization for hit In preclinical studies, showed powerful ERK1/2 inhibitory activities (ERK1/2 IC = 0.
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