Intracellular signals

Forgacs G 1995 On the possible role of cytoskeletal filamentous networks in intracellular signalling J. Ceii. Sc/. 108 2131-43... 

Fig. 1. The GP Ib-IX-V complex. The complex consists of seven transmembrane polypeptides denoted GP Iba (mol wt 145,000), GP IbP (mol wt 24,000), GPIX (mol wt 17,000) and GP V (mol wt 82,000), in a stoichiometry of 2 2 2 1. The hatched region represents the plasma membrane. The area above the hatched region represents the extracellular space that below represents the cytoplasm. The complex is a major attachment site between the plasma membrane and the cytoskeleton. Two molecules associated with the cytoplasmic domain are depicted a 14-3-3 dimer, which may mediate intracellular signaling, and actin-binding protein, which connects the complex to the cortical cytoskeleton and fixes its position and influences its function.

There are five known classes of enzyme-linked receptors (1) receptor tyrosine kinases, which phosphorylate specific tyrosine residues on intracellular signaling proteins (2) tyrosine kinase-associated receptors, such as the prolactin and growth hormone receptors we have already discussed, which... 

The augmentation of a p sheet in one protein by a strand emanating from another is a mode of protein association not restricted to viral shells. Small domains involved in intracellular signal transduction bind to "arms" of other proteins by presenting the edge of a sheet on which those arms can form an additional strand. 

Grb-2 facilitates the transduction of an extracellular stimulus to an intracellular signaling pathway, (b) The adaptor protein PSD-95 associates through one of its three PDZ domains with the N-methyl-D-aspartic acid (NMDA) receptor. Another PDZ domain associates with a PDZ domain from neuronal nitric oxide synthase (nNOS). Through its interaction with PSD-95, nNOS is localized to the NMDA receptor. Stimulation by glutamate induces an influx of calcium, which activates nNOS, resulting in the production of nitric oxide. 

The antiinflammatory effects of statins likely result from their ability to inhibit the formation of mevalonic acid. Downstream products of this molecule include not only the end product, cholesterol, but also several isoprenoid intermediates that covalently modify ( pre-nylate ) certain key intracellular signaling molecules. Statin treatment reduces leukocyte adhesion, accumulation of macrophages, MMPs, tissue factor, and other proinflammatory mediators. By acting on the MHC class II transactivator (CIITA), statins also interfere with antigen presentation and subsequent T-cell activation. Statin treatment can also limit platelet activation in some assays as well. All these results support the concept that in addition to their favorable effect on the lipid profile, statins can also exert an array of antiinflammatory and immunomodulatory actions. 

Adhesion molecule inhibitors Intracellular signalling targets (eg SMADs)... 

G-protein-coupled receptors (GPCRs), although some of them additionally play a role in intracellular signal transduction. Sphingosine-1-phosphate (SIP) and... 

The Src-homology 2 (SH2) domain is a protein domain of roughly 100 amino acids found in many signaling molecules. It binds to phosphorylated tyrosines, in particular peptide sequences on activated receptor tyrosine kinases or docking proteins. By recognizing specific phosphorylated tyrosines, these small domains serve as modules that enable the proteins that contain them to bind to activated receptor tyrosine kinases or other intracellular signaling proteins that have been transiently phosphorylated on tyrosines. 

Besides classical receptor classes that bind endogenous or naturally occurring ligands and act via prototypical intracellular signaling cascades, a considerable number of transmembrane proteins are referred to as receptors albeit their natural ligands are unknown or they do not... 

The diversity of these subcellular actin structures is remarkable and appears to be determined by the interactions of many actin-binding proteins (ABPs) as well as by changes in the concentrations of intracellular signaling molecules such as Ca and cAMP, by small GTP-binding proteins, and by signals arising from mechanical stress. Approximately 50% of the actin molecules in most animal cells are unpolymerized subunits in the cytosolic pool and exist in a state of dynamic equilibrium with labile F-actin filamentous structures (i.e., new structures are formed while existing structures are renewed) (Hall, 1994). 

The smooth muscle cell does not respond in an all-or-none manner, but instead its contractile state is a variable compromise between diverse regulatory influences. While a vertebrate skeletal muscle fiber is at complete rest unless activated by a motor nerve, regulation of the contractile activity of a smooth muscle cell is more complex. First, the smooth muscle cell typically receives input from many different kinds of nerve fibers. The various cell membrane receptors in turn activate different intracellular signal-transduction pathways which may affect (a) membrane channels, and hence, electrical activity (b) calcium storage or release or (c) the proteins of the contractile machinery. While each have their own biochemically specific ways, the actual mechanisms are for the most part known only in outline. 

Although toxic agents have the potential to cause necrosis, some of them can interfere with intracellular signaling pathways and induce apoptosis instead of necrosis. It seems that organotin(IV) compounds exert their toxic effects involving all these processes. The precise balance of these actions and their outcomes may differ radically from one cell type to another and among different organisms. 

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