RTK KIT regulates a variety of crucial cellular processes via its cytoplasmic (CD) domain composed of the tyrosine kinase domain crowned by highly flexible domains-juxtamembrane region, kinase insert domain and C-tail, key recruitment regions for downstream signalling proteins. We generated the 3D model of the full-length CD attached to the transme...
Published in Bioscience Reports
Protein tyrosine phosphorylation is one of the major post-translational modifications in eukaryotic cells and represents a critical regulatory mechanism of a wide variety of signaling pathways. Aberrant protein tyrosine phosphorylation has been linked to various diseases, including metabolic disorders and cancer. Few years ago, protein tyrosine pho...
Les thérapies ciblant les récepteurs tyrosine kinase ont contribué à améliorer le pronostic de certains patients et apportent un véritable espoir thérapeutique dans la lutte contre les cancers. Bien que la majorité des mutations des RTK impactent le domaine kinase et conduisent à leur activation constitutive, celles touchant le récepteur MET dans l...
Published in Biochemical pharmacology
Acute myelogenous leukaemia (AML) is an aggressive blood cancer characterized by the rapid proliferation of immature myeloid blast cells, resulting in a high mortality rate. The 5-year overall survival rate for AML patients is approximately 25%. Circa 35% of all patients carry a mutation in the FLT3 gene which have a poor prognosis. Targeting FLT3 ...
Published in Journal of hepatology
The tumour microenvironment shapes tumour growth through cellular communications that include both direct interactions and secreted factors. The aim of this study was to characterize the impact of the secreted glycoprotein ADAMTSL5, whose role in cancer has not been previously investigated, on hepatocellular carcinoma (HCC). ADAMTSL5 methylation st...
Published in Scientific Reports
Receptor tyrosine kinases (RTKs) are key regulators of normal cellular processes and have a critical role in the development and progression of many diseases. RTK ligand-induced stimulation leads to activation of the cytoplasmic kinase domain that controls the intracellular signalling. Although the kinase domain of RTKs has been extensively studied...
EphB4 is a receptor protein over-expressed by many different cancers. This study explored the regulation of EphB4 and its binding partner, the ephrin-B2 ligand, in prostate cancer cells. This work showed that both EphB4 and ephrin-B2 can be cleaved by an important prostate cancer associated protease, KLK4 and this regulates the interaction between ...
Published in Gastroenterology
In KIT-mutant GIST, inhibition of PDGFRA disrupts a KIT-ERK-ETV1-KIT signaling loop by inhibiting ERK activation. The PDGFRA inhibitor crenolanib might be used to treat patients with imatinib-resistant, KIT-mutant GIST.
Published in The Journal of biological chemistry
The oncogenic roles of PDGF-D and its proteolytic activator, matriptase, have been strongly implicated in human prostate cancer. Latent full-length PDGF-D (FL-D) consists of a CUB domain, a growth factor domain (GFD), and the hinge region in between. Matriptase processes the FL-D dimer into a GFD dimer (GFD-D) in a stepwise manner, involving genera...
Published in The Journal of biological chemistry
Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective ...
