Phosphoinositide 3-kinase regulates crosstalk between Trk A tyrosine kinase and p75NTR-dependent sphingolipid signaling pathways

2001 ◽  
Vol 76 (5) ◽  
pp. 1540-1551 ◽  
Author(s):  
Tim R. Bilderback ◽  
Valeswara-Rao Gazula ◽  
Rick T. Dobrowsky
Keyword(s):  
Tyrosine Kinase ◽  
Signaling Pathways ◽  
Trk A ◽  
Phosphoinositide 3 Kinase

Classic and Novel Signaling Pathways Involved in Cancer: Targeting the NF-κB and Syk Signaling Pathways

2019 ◽  
Vol 14 (3) ◽  
pp. 219-225 ◽  
Author(s):  
Cong Tang ◽  
Guodong Zhu
Keyword(s):  
Cancer Therapy ◽  
Tyrosine Kinase ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Cell Receptor ◽  
Transmembrane Receptors ◽  
Biological Responses ◽  
Different Types

The nuclear factor kappa B (NF-κB) consists of a family of transcription factors involved in the regulation of a wide variety of biological responses. Growing evidence support that NF-κB plays a major role in oncogenesis as well as its well-known function in the regulation of immune responses and inflammation. Therefore, we made a review of the diverse molecular mechanisms by which the NF-κB pathway is constitutively activated in different types of human cancers and the potential role of various oncogenic genes regulated by this transcription factor in cancer development and progression. We also discussed various pharmacological approaches employed to target the deregulated NF-κB signaling pathway and their possible therapeutic potential in cancer therapy. Moreover, Syk (Spleen tyrosine kinase), non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immune-receptors like the B-cell receptor (BCR), which can also activate the inflammasome and NF-κB-mediated transcription of chemokines and cytokines in the presence of pathogens would be discussed as well. The highlight of this review article is to summarize the classic and novel signaling pathways involved in NF-κB and Syk signaling and then raise some possibilities for cancer therapy.

Phosphoinositide 3-kinase and integrin signalling are involved in activation of Bruton tyrosine kinase in thrombin-stimulated platelets

FEBS Letters ◽  
1999 ◽  
Vol 443 (1) ◽  
pp. 66-70 ◽  
Author(s):  
Muriel Laffargue ◽  
Jeannie M.F. Ragab-Thomas ◽  
Ashraf Ragab ◽  
Joel Tuech ◽  
Karine Missy ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Bruton Tyrosine Kinase ◽  
Phosphoinositide 3 Kinase

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 Signaling Pathways That Regulate Normal and Aberrant Red Blood Cell Development

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1646
Author(s):  
Mark C. Wilkes ◽  
Aya Shibuya ◽  
Kathleen M. Sakamoto
Keyword(s):  
Blood Cell ◽  
Signaling Pathways ◽  
Therapeutic Potential ◽  
Cell Development ◽  
Signaling Cascades ◽  
Hematopoietic Stem ◽  
Multiple Substrates ◽  
Stem And Progenitor Cells ◽  
Multiple Copies ◽  
Phosphoinositide 3 Kinase

Blood cell development is regulated through intrinsic gene regulation and local factors including the microenvironment and cytokines. The differentiation of hematopoietic stem and progenitor cells (HSPCs) into mature erythrocytes is dependent on these cytokines binding to and stimulating their cognate receptors and the signaling cascades they initiate. Many of these pathways include kinases that can diversify signals by phosphorylating multiple substrates and amplify signals by phosphorylating multiple copies of each substrate. Indeed, synthesis of many of these cytokines is regulated by a number of signaling pathways including phosphoinositide 3-kinase (PI3K)-, extracellular signal related kinases (ERK)-, and p38 kinase-dependent pathways. Therefore, kinases act both upstream and downstream of the erythropoiesis-regulating cytokines. While many of the cytokines are well characterized, the nuanced members of the network of kinases responsible for appropriate induction of, and response to, these cytokines remains poorly defined. Here, we will examine the kinase signaling cascades required for erythropoiesis and emphasize the importance, complexity, enormous amount remaining to be characterized, and therapeutic potential that will accompany our comprehensive understanding of the erythroid kinome in both healthy and diseased states.

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.

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