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Signal transduction

About: Signal transduction is a research topic. Over the lifetime, 122628 publications have been published within this topic receiving 8209258 citations. The topic is also known as: GO:0007165.


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Journal ArticleDOI
TL;DR: Recent findings on the cellular and molecular mechanisms by which ROS signal events leading to impairment of endothelial barrier function and promotion of leukocyte adhesion are discussed.
Abstract: Reactive oxygen species (ROS) are generated at sites of inflammation and injury, and at low levels, ROS can function as signaling molecules participating as signaling intermediates in regulation of fundamental cell activities such as cell growth and cell adaptation responses, whereas at higher concentrations, ROS can cause cellular injury and death. The vascular endothelium, which regulates the passage of macromolecules and circulating cells from blood to tissues, is a major target of oxidant stress, playing a critical role in the pathophysiology of several vascular diseases and disorders. Specifically, oxidant stress increases vascular endothelial permeability and promotes leukocyte adhesion, which are coupled with alterations in endothelial signal transduction and redox-regulated transcription factors such as activator protein-1 and nuclear factor-κB. This review discusses recent findings on the cellular and molecular mechanisms by which ROS signal events leading to impairment of endothelial barrier fun...

760 citations

Journal ArticleDOI
TL;DR: In this article, the function of the canonical Notch-RBP-J pathway in dendritic cell (DC) development and maintenance was investigated in vivo. But, the authors did not find that RBP-J-deficient splenic CD8(-) DCs were depleted at the postprogenitor stage, exhibited increased apoptosis, and lost the expression of the Notch target gene Deltex1.
Abstract: Signaling through Notch receptors and their transcriptional effector RBP-J is essential for lymphocyte development and function, whereas its role in other immune cell types is unclear. We tested the function of the canonical Notch-RBP-J pathway in dendritic cell (DC) development and maintenance in vivo. Genetic inactivation of RBP-J in the bone marrow did not preclude DC lineage commitment but caused the reduction of splenic DC fraction. The inactivation of RBP-J in DCs using a novel DC-specific deleter strain caused selective loss of the splenic CD8(-) DC subset and reduced the frequency of cytokine-secreting CD8(-) DCs after challenge with Toll-like receptor ligands. In contrast, other splenic DC subsets and DCs in the lymph nodes and tissues were unaffected. The RBP-J-deficient splenic CD8(-) DCs were depleted at the postprogenitor stage, exhibited increased apoptosis, and lost the expression of the Notch target gene Deltex1. In the spleen, CD8(-) DCs were found adjacent to cells expressing the Notch ligand Delta-like 1 in the marginal zone (MZ). Thus, canonical Notch-RBP-J signaling controls the maintenance of CD8(-) DCs in the splenic MZ, revealing an unexpected role of the Notch pathway in the innate immune system.

759 citations

Journal ArticleDOI
TL;DR: The introduction of endocrine disrupting compounds into the environment that mimic or alter the actions of estradiol has generated considerable concern, and the developing brain is a particularly sensitive target.
Abstract: Estradiol is the most potent and ubiquitous member of a class of steroid hormones called estrogens. Fetuses and newborns are exposed to estradiol derived from their mother, their own gonads, and synthesized locally in their brains. Receptors for estradiol are nuclear transcription factors that regulate gene expression but also have actions at the membrane, including activation of signal transduction pathways. The developing brain expresses high levels of receptors for estradiol. The actions of estradiol on developing brain are generally permanent and range from establishment of sex differences to pervasive trophic and neuroprotective effects. Cellular end points mediated by estradiol include the following: 1) apoptosis, with estradiol preventing it in some regions but promoting it in others; 2) synaptogenesis, again estradiol promotes in some regions and inhibits in others; and 3) morphometry of neurons and astrocytes. Estradiol also impacts cellular physiology by modulating calcium handling, immediate-early-gene expression, and kinase activity. The specific mechanisms of estradiol action permanently impacting the brain are regionally specific and often involve neuronal/glial cross-talk. The introduction of endocrine disrupting compounds into the environment that mimic or alter the actions of estradiol has generated considerable concern, and the developing brain is a particularly sensitive target. Prostaglandins, glutamate, GABA, granulin, and focal adhesion kinase are among the signaling molecules co-opted by estradiol to differentiate male from female brains, but much remains to be learned. Only by understanding completely the mechanisms and impact of estradiol action on the developing brain can we also understand when these processes go awry.

759 citations

Journal ArticleDOI
TL;DR: The need to characterize individual TLR at the very beginning of signal initiation in order to understand their diverse biological functions is stressed.
Abstract: Recognition by innate immune cells of the pathogen associated molecular patterns (PAMP) lipopolysaccharide (LPS) from Gram-negative bacteria and bacterial CpG-DNA depends on Toll-like receptor4 (TLR4) and TLR9, respectively. To define differences in the response to these distinct PAMP we compared a key intracellular event, namely recruitment of myeloid differentiation marker 88 (MyD88) to the respective PAMP-initiated TLR signaling. Using MyD88-GFP fusion protein expressing macrophages we demonstrate that LPS and CpG-DNA trigger signaling from two different cellular locations: theformer at the cell membrane and the latter at the lysosomal compartment. While LPS does not require endocytosis to functionally associate with the membrane expressed TLR4/MD2 complex, internalization and endosomal maturation is conditional for CpG-DNA to activate TLR9. In support of these data TLR9 is not localized at the cell surface, but intracellularily. These data stress the need to characterize individual TLR at the very beginning of signal initiation in order to understand their diverse biological functions.

758 citations

Journal ArticleDOI
TL;DR: The Th17 response can promote tumor growth, in part via an IL-6–Stat3 pathway, and adoptive transfer studies and analysis of the tumor microenvironment suggest that CD4+ T cells are the predominant source of IL-17.
Abstract: Although the Th17 subset and its signature cytokine, interleukin (IL)-17A (IL-17), are implicated in certain autoimmune diseases, their role in cancer remains to be further explored. IL-17 has been shown to be elevated in several types of cancer, but how it might contribute to tumor growth is still unclear. We show that growth of B16 melanoma and MB49 bladder carcinoma is reduced in IL-17−/− mice but drastically accelerated in IFN-γ−/− mice, contributed to by elevated intratumoral IL-17, indicating a role of IL-17 in promoting tumor growth. Adoptive transfer studies and analysis of the tumor microenvironment suggest that CD4+ T cells are the predominant source of IL-17. Enhancement of tumor growth by IL-17 involves direct effects on tumor cells and tumor-associated stromal cells, which bear IL-17 receptors. IL-17 induces IL-6 production, which in turn activates oncogenic signal transducer and activator of transcription (Stat) 3, up-regulating prosurvival and proangiogenic genes. The Th17 response can thus promote tumor growth, in part via an IL-6–Stat3 pathway.

758 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20232,989
20225,166
20213,971
20204,179
20194,445
20184,585