Topic
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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TL;DR: This picture argues powerfully that, for therapy of brain ischemia and reperfusion, the concept of single drug intervention cannot be effective.
778 citations
TL;DR: It is concluded that chemerin is a novel adipose-derived signaling molecule that regulates adipogenesis and adipocyte metabolism and has a role in adaptive and innate immunity.
778 citations
TL;DR: It is indicated that AKT activation is one of the most common molecular alterations in human malignancy, and efforts to target molecular components of the AKT pathway for cancer therapy and, possibly, cancer prevention are considered.
Abstract: The AKT1, AKT2, and AKT3 kinases have emerged as critical mediators of signal transduction pathways downstream of activated tyrosine kinases and phosphatidylinositol 3-kinase. An ever-increasing list of AKT substrates has precisely defined the multiple functions of this kinase family in normal physiology and disease states. Cellular processes regulated by AKT include cell proliferation and survival, cell size and response to nutrient availability, intermediary metabolism, angiogenesis, and tissue invasion. All these processes represent hallmarks of cancer, and a burgeoning literature has defined the importance of AKT alterations in human cancer and experimental models of tumorigenesis, continuing the legacy represented by the original identification of v-Akt as the transforming oncogene of a murine retrovirus. Many oncoproteins and tumor suppressors intersect in the AKT pathway, finely regulating cellular functions at the interface of signal transduction and classical metabolic regulation. This careful balance is altered in human cancer by a variety of activating and inactivating mechanisms that target both AKT and interrelated proteins. Reprogramming of this altered circuitry by pharmacologic modulation of the AKT pathway represents a powerful strategy for rational cancer therapy. In this review, we summarize a large body of data, from many types of cancer, indicating that AKT activation is one of the most common molecular alterations in human malignancy. We also review mechanisms of activation of AKT kinases, examples of therapeutic modulation of the AKT pathway in animal models, and the current status of efforts to target molecular components of the AKT pathway for cancer therapy and, possibly, cancer prevention.
778 citations
TL;DR: It is shown that the NPR1 paralogues NPR3 and NPR4 are SA receptors that bind SA with different affinities, and that this mutant is defective in pathogen effector-triggered programmed cell death and immunity.
Abstract: Salicylic acid (SA) is a plant immune signal produced after pathogen challenge to induce systemic acquired resistance. It is the only major plant hormone for which the receptor has not been firmly identified. Systemic acquired resistance in Arabidopsis requires the transcription cofactor nonexpresser of PR genes 1 (NPR1), the degradation of which acts as a molecular switch. Here we show that the NPR1 paralogues NPR3 and NPR4 are SA receptors that bind SA with different affinities. NPR3 and NPR4 function as adaptors of the Cullin 3 ubiquitin E3 ligase to mediate NPR1 degradation in an SA-regulated manner. Accordingly, the Arabidopsis npr3 npr4 double mutant accumulates higher levels of NPR1, and is insensitive to induction of systemic acquired resistance. Moreover, this mutant is defective in pathogen effector-triggered programmed cell death and immunity. Our study reveals the mechanism of SA perception in determining cell death and survival in response to pathogen challenge. Plant resistance to pathogen challenge is thought to be mediated through salicylic acid (SA) signalling; here NPR3 and NPR4, paralogues of the transcription cofactor NPR1, are identified as receptors of SA. Salicylic acid is the only major plant hormone for which a receptor has not been firmly identified. It is produced in plants in response to pathogen challenge, and induces systemic acquired resistance against secondary infection. This process requires the transcription cofactor NPR1, which indicated that NPR1 might be a salicylic acid receptor, but NPR1 alone does not bind to the hormone. Here, Xinnian Dong and colleagues identify the NPR1 paralogues NPR3 and NPR4 as salicylic acid receptors with different binding affinities. The authors propose a model for the regulation of NPR1 by NPR3 and NPR4 in response to different levels of salicylic acid.
778 citations
TL;DR: In this paper, the role of mammalian Toll-like receptors (TLRs) as signal transducers for LPS was investigated, and it was shown that LPS signaling through TLR2 was dependent on serum which contains soluble CD14 (sCD14).
Abstract: Bacterial lipopolysaccharide (LPS) induces activation of the transcription factor nuclear factor kappaB (NF-kappaB) in host cells upon infection. LPS binds to the glycosylphosphatidylinositol (GPI)- anchored membrane protein CD14, which lacks an intracellular signaling domain. Here we investigated the role of mammalian Toll-like receptors (TLRs) as signal transducers for LPS. Overexpression of TLR2, but not TLR1, TLR4, or CD14 conferred LPS inducibility of NF-kappaB activation in mammalian 293 cells. Mutational analysis demonstrated that this LPS response requires the intracellular domain of TLR2. LPS signaling through TLR2 was dependent on serum which contains soluble CD14 (sCD14). Coexpression of CD14 synergistically enhanced LPS signal transmission through TLR2. In addition, purified recombinant sCD14 could substitute for serum to support LPS-induced TLR2 activation. LPS stimulation of TLR2 initiated an interleukin 1 receptor-like NF-kappaB signaling cascade. These findings suggest that TLR2 may be a signaling component of a cellular receptor for LPS.
777 citations