Cellular signaling pathway

Cato AC, Nestl A, Mink S (2002) Rapid actions of steroid receptors in cellular signaling pathways. Sci STKE 2002 RE9. 

Proteasomal degradation also plays an essential role in the activation of cellular signaling pathways. A prototype for this is the control of NF-kB signaling, which has a pivotal role in inflammatory responses. Upon stimulation the inhibitory IicBa protein is phos-phorylated and thereby becomes a target substrate for K48-polyubiquitination. Proteasomal degradation of IkBu releases the transcription factor NF-kB, which subsequently translocates to the nucleus and activates specific target genes. 

Many environmental toxins interact with specific cellular receptors, including enzymes, ion channels and ion pumps, and thus provide natural tools for the study of cellular signalling pathways. Palytoxin, a compound isolated from the coelen-terate of genus Palythoa, is one such useful and intriguing compound. The structure of palytoxin was first determined in 1981 independently by Hirata (7) and Moore (2). As one of the most potent marine toxins known, palytoxin has been studied in a variety of systems ranging from erythrocytes to neurons. As a tumor promoter of the non 12-O-tetradecanoylphorbol-13-acetate (TPA) type, palytoxin can also be studied in the context of a growth control system. 

Thus, the evidence that stress, and the stress hormone corticosterone, may cause changes in hippocampal structure, hippocampal connections, and changes in gene and protein expression, suggest that viable targets of anxiolytic agents are cellular signaling pathways involved in neuroplasticity and the maintenance of cellular resilience. 

Umezawa Y (2005) Genetically encoded optical probes for imaging cellular signaling pathways. Biosens Bioelectron 20 2504-11... 

Coussens, L., Parker, P.J., Rhee, L., Yang-Feng, T.L., Chen, E., Waterfield, M.D., Francke, U., and Ullrich, A., 1986, Multiple, distinct forms ofbovine and human protein kinase C suggest diversity in cellular signaling pathways. Science 233 859-866. 

Wu RC, Qin J, Yi P, Wong J, Tsai SY, Tsai M J, O Malley BW (2004) Selective phosphorylations of the SRC-31AIB 1 coactivator integrate genomic reponses to multiple cellular signaling pathways. Mol Cell 15 937-949... 

Finally, there are ion channels that respond to intracellular (as opposed to extracellular or environmental) chemical stimuli. These form part of cellular signaling pathways and may be opened by cellular messengers such as calcium ion, Ca +. Such channels are known as signal-gated ion channels. 

Up to 30% of cancers Involve mutations ofRas, a small GTPase that regulates the cell cycle and cellular signaling pathways In response to growth factors (see Chapter 14). 

Hazel, B.A., O Connor, A., Niculescu, R. Kalf, GF. (1995) Benzene and its metabolite, hydroquinone, induce granulocytic differentiation in myeloblasts by interacting with cellular signaling pathways activated by granulocyte colony-stimulating factor. Stem Cells, 13, 295-310... 

Dietary Isoflavones Cardiovascular Actions and Activation of Cellular Signaling Pathways... 

ACTIVATION OF CELLULAR SIGNALING PATHWAYS AND ANTIOXIDANT DEFENSE GENES BY ISOFLAVONES... 

The PI3-K/PKB pathway is another key cellular signaling pathway that plays an important role in cell growth, survival, proliferation, and gene expression. PKB, also known as Akt, exists in three isoforms PKBa/Aktl, PKB(3/Akt2, and PKBy/Akt3 each isoform possesses an amino-terminal PH domain, a kinase... 

The failure of antioxidant mechanisms to correct redox disequilibrium could lead to the escalation of oxidative to tier 2. Tier 2 cellular responses are characterized by the activation of cellular signaling pathway such as stress-activated kinases (p38 MAP kinase and JNK) along with activation and nuclear translocation of transcription factors NF-kB and STAT-1. NF-KB-induced transcriptional activation leads to the production of a number of pro-inflammatory cytokines, including the neutrophil chemoattractant IL-8. STAT-1 activation stimulates the increased production of CXC-motif chemokines that function in lymphocyte recruitment and activation. Therefore, tier 2 oxidative responses result in an inflammatory response in the lung. 

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