Differences in signaling pathways and expression level of the phosphoinositide phosphatase SHIP1 between two oncogenic mutants of the receptor tyrosine kinase KIT

2006 ◽  
Vol 18 (5) ◽  
pp. 661-669 ◽  
Author(s):  
J.M. Vanderwinden ◽  
D. Wang ◽  
N. Paternotte ◽  
S. Mignon ◽  
K. Isozaki ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Signaling Pathways ◽  
Receptor Tyrosine Kinase ◽  
Expression Level ◽  
Phosphoinositide Phosphatase

scholarly journals Helicobacter Pylori Targets the EPHA2 Receptor Tyrosine Kinase in Gastric Cells Modulating Key Cellular Functions

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 513 ◽  
Author(s):  
Marina Leite ◽  
Miguel S. Marques ◽  
Joana Melo ◽  
Marta T. Pinto ◽  
Bruno Cavadas ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Tyrosine Kinase ◽  
Signaling Pathways ◽  
Receptor Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Receptor Activation ◽  
Degradation Pathway ◽  
Mrna Levels ◽  
H Pylori

Helicobacter pylori, a stomach-colonizing Gram-negative bacterium, is the main etiological factor of various gastroduodenal diseases, including gastric adenocarcinoma. By establishing a life-long infection of the gastric mucosa, H. pylori continuously activates host-signaling pathways, in particular those associated with receptor tyrosine kinases. Using two different gastric epithelial cell lines, we show that H. pylori targets the receptor tyrosine kinase EPHA2. For long periods of time post-infection, H. pylori induces EPHA2 protein downregulation without affecting its mRNA levels, an effect preceded by receptor activation via phosphorylation. EPHA2 receptor downregulation occurs via the lysosomal degradation pathway and is independent of the H. pylori virulence factors CagA, VacA, and T4SS. Using small interfering RNA, we show that EPHA2 knockdown affects cell–cell and cell–matrix adhesion, invasion, and angiogenesis, which are critical cellular processes in early gastric lesions and carcinogenesis mediated by the bacteria. This work contributes to the unraveling of the underlying mechanisms of H. pylori–host interactions and associated diseases. Additionally, it raises awareness for potential interference between H. pylori infection and the efficacy of gastric cancer therapies targeting receptors tyrosine kinases, given that infection affects the steady-state levels and dynamics of some receptor tyrosine kinases (RTKs) and their signaling pathways.

scholarly journals Registered report: Widespread potential for growth factor-driven resistance to anticancer kinase inhibitors

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Edward Greenfield ◽  
Erin Griner ◽  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Signaling Pathways ◽  
Receptor Tyrosine Kinase ◽  
Cancer Biology ◽  
Kinase Inhibitors ◽  
Open Science ◽  
Downstream Signaling ◽  
Rtk Inhibitors ◽  
Block Sensitivity

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of 50 papers in the field of cancer biology published between 2010 and 2012. This Registered Report describes the proposed replication plan of key experiments from ‘Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors’ by Wilson and colleagues, published in Nature in 2012 (<xref ref-type="bibr" rid="bib20">Wilson et al., 2012</xref>). The experiments that will be replicated are those reported in Figure 2B and C. In these experiments, Wilson and colleagues show that sensitivity to receptor tyrosine kinase (RTK) inhibitors can be bypassed by various ligands through reactivation of downstream signaling pathways (Figure 2A; <xref ref-type="bibr" rid="bib20">Wilson et al., 2012</xref>), and that blocking the receptors for these bypassing ligands abrogates their ability to block sensitivity to the original RTK inhibitor (Figure 2C; <xref ref-type="bibr" rid="bib20">Wilson et al., 2012</xref>). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife.

scholarly journals A Folate- and Vitamin B12-Deficient Diet Decreases the Latency and Increases the Incidence of Mammary Tumors in MMTV-ErbB2 Transgenic Mice

2021 ◽  
Author(s):  
Zhengzheng Xiao ◽  
Guoliang Yao ◽  
Yongxuan Liu ◽  
Chunling Zhao
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinase ◽  
Vitamin B12 ◽  
Signaling Pathways ◽  
Mammary Tumor ◽  
Receptor Tyrosine Kinase ◽  
Tumor Development ◽  
Deficient Diet ◽  
Tyrosine Kinase 2 ◽  
Folate And Vitamin B12

Abstract There has been controversy regarding folate- and vitamin B12-deficient diet (FVD)-induced hyperhomocysteinemia (HHcy) associated with breast cancer risk in most published epidemiological studies. Thus, the present study designed experiments to assess the causal association between FVD-induced HHcy and mammary tumor risk, as well as to identify the relative underlying mechanism. In this study, mammary tumor development was examined in mouse mammary tumor virus (MMTV)-erb-b2 receptor tyrosine kinase 2 (ErbB2) mice fed with a control AIN-93G diet or a FVD diet. MMTV-ErbB2 mice fed with the FVD diet displayed elevated blood levels of the amino acid homocysteine, a shorter tumor latency and an increased tumor multiplicity compared with the controls. The expression levels of key markers in the receptor tyrosine kinase and estrogen receptor (ER) signaling pathways, including phosphorylated (p)-Akt, p-Erk, p-ERα and Cyclin D1, were elevated in mammary tissues from MMTV-ErbB2 mice fed the FVD diet compared with mice fed with control diet. These data suggested that FVD-induced HHcy may promote mammary tumor development and decrease tumor latency, possibly by activating the epidermal growth factor receptor/ErbB2 and ERα signaling pathways. Therefore, examining the signaling mechanisms and identifying the relative metabolic pathways underlying mammary tumor promotion following FVD-induced HHcy may provide a novel strategy for breast cancer prevention and treatment.

A gain-of-function mutation in Drosophila MAP kinase activates multiple receptor tyrosine kinase signaling pathways

Cell ◽  
1994 ◽  
Vol 76 (5) ◽  
pp. 875-888 ◽  
Author(s):  
Damian Brunner ◽  
Nadja Oellers ◽  
Janos Szabad ◽  
William H. Biggs ◽  
S.Lawrence Zipursky ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Map Kinase ◽  
Signaling Pathways ◽  
Receptor Tyrosine Kinase ◽  
Kinase Signaling ◽  
Gain Of Function ◽  
Tyrosine Kinase Signaling ◽  
Multiple Receptor

The Drosophila 14–3-3 protein Leonardo enhances Torso signaling through D-Raf in a Ras 1-dependent manner

Development ◽  
1997 ◽  
Vol 124 (20) ◽  
pp. 4163-4171 ◽  
Author(s):  
W. Li ◽  
E.M. Skoulakis ◽  
R.L. Davis ◽  
N. Perrimon
Keyword(s):  
Tyrosine Kinase ◽  
Signaling Pathways ◽  
Receptor Tyrosine Kinase ◽  
Dependent Manner ◽  
Tor Signaling ◽  
Rtk Signaling ◽  
Maternal Expression ◽  
Essential Components ◽  
Precise Role

14-3-3 proteins have been shown to interact with Raf-1 and cause its activation when overexpressed. However, their precise role in Raf-1 activation is still enigmatic, as they are ubiquitously present in cells and found to associate with Raf-1 in vivo regardless of its activation state. We have analyzed the function of the Drosophila 14–3-3 gene leonardo (leo) in the Torso (Tor) receptor tyrosine kinase (RTK) pathway. In the syncytial blastoderm embryo, activation of Tor triggers the Ras/Raf/MEK pathway that controls the transcription of tailless (tll). We find that, in the absence of Tor, overexpression of leo is sufficient to activate tll expression. The effect of leo requires D-Raf and Ras1 activities but not KSR or DOS, two recently identified essential components of Drosophila RTK signaling pathways. Tor signaling is impaired in embryos derived from females lacking maternal expression of leo. We propose that binding to 14–3-3 by Raf is necessary but not sufficient for the activation of Raf and that overexpressed Drosophila 14–3-3 requires Ras1 to activate D-Raf.

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