Cell function signal transduction

Includes structural biology, mass spectrometry, protein arrays, bioinformatics, high throughput screening (HTS) assays, protein chemistry, cell biology, signal transduction, and physiology, as related to functional and structural proteomics and methods papers. 

Connective tissue in the vascular system plays an important role in maintenance of the intact vascular wall. Vitamins E and C influence the extracellular matrix (ECM) by their antioxidant functions. They bind to specific enzymes and act as cofactors and regulators with consequent modulation of vascular smooth muscle cell (VSMC) signal transduction and gene expression. The ability of vitamins E and C to influence VSMC proliferation, differentiation, and ECM production is important in the maintenance of intact vascular wall and in the repair of atherosclerotic lesions. Actively proliferating cells, but not quiescent cells, are susceptible to ascorbic acid, which inhibits cell division and promotes necrosis through its action on S-phase progression. 

Depletion of ATP in the cells prevents maintenance of the membrane potential, inhibits the functioning of ion pumps, and attenuates cellular signal transduction (e.g., formation of second messengers such as inositol phos phates or cyclic AMP). A marked ATP depletion ultimately impairs the activ-itv of the cell and leads to ceil death. 

Cells make use of many different types of membranes. All cells have a cytoplasmic membrane, or plasma membrane, that functions (in part) to separate the cytoplasm from the surroundings. In the early days of biochemistry, the plasma membrane was not accorded many functions other than this one of partition. We now know that the plasma membrane is also responsible for (1) the exclusion of certain toxic ions and molecules from the cell, (2) the accumulation of cell nutrients, and (3) energy transduction. It functions in (4) cell locomotion, (5) reproduction, (6) signal transduction processes, and (7) interactions with molecules or other cells in the vicinity. 

CNG channels are expressed in retinal photoreceptors and olfactory neurons, and play a key role in visual and olfactory signal transduction. In addition, CNG channels are found at low density in some other cell types and tissues such as brain, testis, and kidney. While the function of CNG channels in sensory neurons has been unequivocally demonstrated, the role of these channels in other cell types, where expression has been observed, remains to be established. Based on their phylogenetic relationship, the six CNG channels... 

The VACM-1 receptor is a membrane-associated protein with a single putative transmembrane domain that binds selectively AVP (XD — 2 nM), but cannot discriminate between VXR and V2R analogues. It is expressed in endothelial and medullary collecting duct cells and upon stimulation by AVP. It induces a mobilization of cytosolic-free Ca2+, decreases cAMP production and inhibits cellular growth via MAPK phosphorylation and p53 expression. The mechanism of action and physiological functions of this new receptor are not well understood, but it seems to participate in the regulation of AVP induced signal transduction pathways or of a yet unidentified peptide. 

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

Kijima T, Maulik G, Ma PC, et al. Regulation of cellular proliferation, cytoskeletal function and signal transduction through CXCR4 and c-kit in small cell lung cancer cells. Cancer Res 2002 62 6304-6311. 

These are considered to be functionally competent protein domains owing to their ability to maintain their structure and molecular recognition properties independent of the full-length protein (Cohen GB, Ren R, Baltimore D. Modular binding domains in signal transduction proteins. Cell 1995 80 237-248). 

Zhou, Z., Gartner, A., Cade, R., Ammerer, G., and Errede, B. (1993). Pheromone-induced signal transduction in Saccharomyces cerevisiae requires the sequential function of three protein kinases. Mol. Cell. Biol. 13 2069-2080. 

---