Inositol cell signaling

Phosphatidylinositol (abbreviated Ptdlns, or PI) is a minor class of phospholipids composed of glycerol, fatty acids and inositol. Pis are found in the cytosolic side of eukaryotic cell membranes. They are substrates fora large number of enzymes which are involved in cell signalling. 

Li+ causes malformation and affects regeneration in some protozoans, for example Tetrahymenapyriformis [231], by inhibiting both DNA and RNA synthesis by affecting regeneration in Hydra [232], planarians [233], and annelids [234] and by affecting cell signaling mediated by both inositol phosphate metabolism [235] and adenylate cyclase [236] in slime molds. 

The coupling of superantigen—major histocompatibility complex class II to T-cell receptor swifdy results in cell-signaling cascades. ° These staphylococcal toxins can increase levels of phosphatidyl inositol from quiescent T cells, such as other mitogens, as well as elicit intracellular Ca movement that activates the protein kinase C (PKC) pathway important for interleukin-2 (IL-2) expression. " IL-2 is intimately linked to T-cell proliferation. In addition to the PKC pathway, the protein tyrosine kinase (PTK) pathway is also activated by superantigens, leading to elevated expression of various proinflammatory cytokines. Staphylococcal superantigens also potently activate transcriptional factors NF-/IB (nuclear factor kappa B) and AP-1 (activator protein-1), which subsequently elicit the synthesis of proinflammatory cytokines. " " ... 

Berridge MJ Inositol trisphosphate, calcium, lithium, and cell signaling. JAMA 262 1834-1841, 1989... 

The biological effects of histamine (Table 15.1) are mediated via three receptor subtypes, HI, H2 and H3 that are linked to G protein but activate different cell-signalling systems. The histamine HI receptor is associated with the phospholipase C-catalysed formation of inositol 1,4,5-triphosphate (IP3) and 1,2-diacylglycerol (DAG). The H2-receptor is coupled to adenylyl cyclase, increasing the production of cAMP. The cellular messenger system involved in H3-receptor activation has not been fully defined, but it may couple to N-type Ca2+-channels. The genes encoding for HI and H2 receptors have been cloned. A mutation of the human H2 receptor has been linked to schizophrenia. 

C. P. Downes, Inositol Lipids in Cell Signaling, Academic Press, New York,... 

Shears, S.B., 2001, Assessing the omnipotence of inositol hexakisphosphate. Cell Signal. 13 151-158. 

Berridge, M.J., and Irvine, R.F., 1989, Inositol phosphates and cell signaling. Nature 341 388-389. 

Downes, C.P., Gray, A., Watt, S.A. and Lucocq, J.M., 2003, Advances in procedures for the detection and localization of inositol phospholipid signals in cells, tissues, and enzyme assays. Meth. Enz. 366 64-84. 

Src is a oncogene first found in the Rous sarcoma virus where it encodes the pp60 kinase. The corresponding cellular kinase is pp60 -s =. The Src kinases are regulated by phosphorylation de-phosphorylation. Members of the Src family of cytosolic tyrosine kinases with important funtions in cell signalling are for example Yes, Fyn, Lck, Blk, Btk, Csk, Hck, Fgr and Yrk. Fyn associates with the p85 subunit of 1-phosphatidyl inositol... 

Irvine, R.F. (1992). Inositol phosphates in cell signalling. Curr. Opinion in Cell Biol. 4, 212 219. 

The birth of receptor-stimulated inositol polyphosphate metabolism and its role in cell signaling was the observation in the early 1950s of acetylcholine-stimulated P incorporation into inositol lipids (termed the PI response ) (3). However, it would take more than two decades for the mechanisms and significance of this response to come to light. Key to the eventual elucidation of the PI response was... 

Saiardi A, Caffrey JJ, Snyder SH, Shears SB. The inositol hexakisphosphate kinase family. Catalytic flexibility and function in yeast vacuole biogenesis. J. Biol. Chem. 2000 275 24686-24692. Choi K, Mollapour E, Shears SB. Signal transduction during environmental stress InsP8 operates within highly restricted contexts. Cell Signal. 2005 17 1533-1541. 

M.J. Berridge and R.F. Irvine. 1989. Inositol phosphates and cell signalling Aatwre 341 197-205. (PubMedl M.J. Berridge. 1993. Inositol trisphosphate and calcium signalling Aatwre 361 315-325. (PubMedl... 

---