Search results for " Protein-Tyrosine Kinases"
showing 9 items of 59 documents
Antagonistic feedback loops involving Rau and Sprouty in the Drosophila eye control neuronal and glial differentiation.
2013
During development, differentiation is often initiated by the activation of different receptor tyrosine kinases (RTKs), which results in the tightly regulated activation of cytoplasmic signaling cascades. In the differentiation of neurons and glia in the developing Drosophila eye, we found that the proper intensity of RTK signaling downstream of fibroblast growth factor receptor (FGFR) or epidermal growth factor receptor required two mutually antagonistic feedback loops. We identified a positive feedback loop mediated by the Ras association (RA) domain-containing protein Rau that sustained Ras activity and counteracted the negative feedback loop mediated by Sprouty. Rau has two RA domains t…
TGFβ-induced EMT requires focal adhesion kinase (FAK) signaling
2007
The epithelial-to-mesenchymal transition (EMT) is a crucial process, occurring both during development and tumor progression, by which an epithelial cell undergoes a conversion to a mesenchymal phenotype, dissociates from initial contacts and migrates to secondary sites. We recently reported that in hepatocytes the multifunctional cytokine TGFβ induces a full EMT characterized by (i) Snail induction, (ii) E-cadherin delocalization and down-regulation, (iii) down-regulation of the hepatocyte transcriptional factor HNF4α and (iv) up-regulation of mesenchymal and invasiveness markers. In particular, we showed that Snail directly causes the transcriptional down-regulation of E-cadherin and HN…
Interactions between cholinergic and fibroblast growth factor receptors in brain trophism and plasticity
2014
Acetylcholine, acting on both nicotinic receptors (nAChRs) and muscarinic receptors (mAChRs), plays a role in the regulation of synaptic plasticity, being involved in the regulation of cellular processes and cognitive functions, such as learning, memory and attention. Recently, G protein coupled receptors (GPCRs), including mAChRs, have been reported to transactivate tyrosine-kinase receptors (RTK), such as epidermal growth factor receptor (EGFR), and initiate their intracellular signaling. In this minireview we have first analysed the RTK transactivation mechanisms, involving cholinergic receptors, and thereafter the interplay between AChR and neurotrophic factor systems built up by FGF2 a…
Predicting efficacy and toxicity in the era of targeted therapy: focus on anti-EGFR and anti-VEGF molecules
2011
The treatment of solid malignancies includes various target drugs, such as monoclonal antibodies and tyrosine kinase inhibitors, which exert their effect alone or in combination with chemotherapy. The main part of these molecules have a target on proteins of EGFR and VEGF pathways. The particular toxicity profile and the financial impact, deriving from the application of these agents in cancer treatment, prompted a lot of researches to define predictive factors of their efficacy. Various biomarker were identified among the components of the targeted pathways. However just few studies allowed to identify specific factors to predict the toxicity of these drugs. In this review EGFR and VEGF-re…
Wee1 inhibition potentiates Wip1-dependent p53-negative tumor cell death during chemotherapy
2016
AbstractInactivation of p53 found in more than half of human cancers is often associated with increased tumor resistance to anti-cancer therapy. We have previously shown that overexpression of the phosphatase Wip1 in p53-negative tumors sensitizes them to chemotherapeutic agents, while protecting normal tissues from the side effects of anti-cancer treatment. In this study, we decided to search for kinases that prevent Wip1-mediated sensitization of cancer cells, thereby interfering with efficacy of genotoxic anti-cancer drugs. To this end, we performed a flow cytometry-based screening in order to identify kinases that regulated the levels of γH2AX, which were used as readout. Another criter…
Activation of TRK Genes in Ewingʼs Sarcoma Trk A Receptor Expression Linked to Neural Differentiation
1997
Trk receptors have been identified by immunohistochemical methods in primitive neuroectodermal tumor (PNET)/Ewing's sarcoma (ES). However, the presence of different members of the Trk family of receptors in PNET/ES has not been specified. We have examined whether Trk A, B, and C receptors are specifically expressed in ES both with and without features of neural differentiation. Ten ES tumors (five primary tumors of bone and five extraosseous tumors transplanted into nude mice) were investigated for expression of Trk receptors by immunohistochemistry and reverse transcription-polymerase chain reaction. One primary ES and the five grafted ES tumors exhibited signs of neural differentiation; t…
Expression of neurotrophins, GDNF, and their receptors in rat thyroid tissue
1999
Levels of mRNA for neurotrophins (brain-derived neurotrophic factor, BDNF; neurotrophin 3, NT-3; neurotrophin 4, NT-4) and their receptors (trkA, trkB, trkC) and for glial cell line-derived neurotrophic factor (GDNF) and its receptors (ret, GDNFR-alpha) were measured in rat thyroid tissue by ribonuclease protection assays. In thyroid tissue the NT-3 mRNA level was threefold lower and the NT-4 mRNA level sixfold higher than those detected in adult rat hippocampus, while BDNF mRNA was undetectable. Very low levels of mRNA for truncated trkB and trkC receptors and no catalytic trkA, trkB or trkC were found. In conclusion NT-3 and NT-4, but not the corresponding functional receptors, are expres…
Aberrant copy numbers of ALK gene is a frequent genetic alteration in neuroblastomas.
2009
A total of 50 neuroblastomas were assessed for frequency of ALK gene copy number aberrations by interphase fluorescence in situ hybridization using a break-apart fluorescence in situ hybridization probe. The data were compared with status of MYCN, 11q, 17q, and 1p36. We observed ALK aberrations (amplification, 1 of 45; gain, 15 of 45 and loss/imbalance, 11 of 45) in a total of 27 (60%) of 45 neuroblastomas. Synchronic MYCN and ALK aberrations accounted for 23 of 45 (51%) tumors; however, MYCN alterations were also detected in 11 (60%) of 18 tumors without ALK aberrations. Our data suggest that copy number aberrations of the ALK gene is a frequent genetic event in the development of neurobla…
Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN 2A and FMTC.
1994
We have analysed 118 families with inherited medullary thyroid carcinoma (MTC) for mutations of the RET proto-oncogene. These included cases of multiple endocrine neoplasia types 2A (MEN 2A) and 2B (MEN 2B) and familial MTC (FMTC). Mutations at one of 5 cysteines in the extracellular domain were found in 97% of patients with MEN 2A and 86% with FMTC but not in MEN 2B patients or normal controls. 84% of the MEN2A mutations affected codon 634. MEN 2A patients with a Cys634 to Arg substitution had a greater risk of developing parathyroid disease than those with other codon 634 mutations. Our data show a strong correlation between disease phenotype and the nature and position of the RET mutatio…