Phosphatidylinositol signaling

Zhang, X., and Majerus, P.W., 1998, Phosphatidylinositol signaling reachons. Semin. Cell. Dev. Biol. 9. 153-160. 

Lin, W.H., Rui, Y.E., Hui, M.A., Xu, Z.H., Xui, H.W., 2004, DNA chip-based expression profile analysis indicates involvement of the phosphatidylinositol signaling pathway in multiple plant responses to hormone and abiotic treatments. Cell Research 14 34-45. 

Atack, J.R., 2000, Lithium, phosphatidylinositol signaling, and bipolar disorder. In Manji, H.K., Bowden, C.L., and Belmaker, R.H. (eds.), Bipolar Medications Mechanism of Action. American Psychiatric Press, Inc., Washington, DC. 

Local anesthetics have a wide range of effects. They inhibit sodium, potassium, and calcium ion channels, alpha-adrenoceptors, and phosphatidylinositol signalling. They also cause dysrhythmias when injected directly into the brain. Local anesthetics are also mitochondrial poisons and impair oxidative phosphorylation. 

Mato, J.M., Giraldez, F., and Varela-Nieto, I. Brain-derived neurotrophic factor and neurotrophin-3 induce cell proliferation in the cochleovestibular ganglion through a glycosyl-phosphatidylinositol signaling system. Dev. Biol., 1993, 359,... 

Signal stimulating FSH release Gonadotropin releasing hormone from the hypothalamus binds to membrane receptors of the anterior pituitary cells, triggered phosphatidylinositol signaling to stimulate FSH production and release. 

Zhang, X. Loijens, J.C. Boronenkov, I.V. Parker, G.J. Norris, F.A. Chen, J. Thum, O. Prestwich, G.D. Majerus, P.W. Anderson, R.A. Phosphatidylino-sitol-4-phosphate 5-kinase isozymes catalyze the synthesis of 3-phosphate-containing phosphatidylinositol signaling molecules. J. Biol. Chem., 272, 17756-17761 (1997)... 

Roberts, K Rowlinson, R Smith, J,M Swarbrick, M,E Treinies, I Winter, J.J.G., and Wood, R,J, (2014) Potent, selective small molecule inhibitors of type III phosphatidylinositol-4-kinase a- but not P-inhibit the phosphatidylinositol signaling cascade and cancer cell proliferation. Chemical Communications, 50,... 

Kimata T, Tanizawa Y, Can Y, Ikeda S, Kuhara A, More I. S)maptic polarity depends on phosphatidylinositol signaling regulated by myoinositol monophosphatase in Caenorlmbditis ekgans. Genetics 2012 191 509-21. 

ET-1 also stimulates anti-apoptotic signal cascades in fibroblasts, vascular smooth muscles and endothelial cells (via phosphatidylinositol-3-kinase and Akt/pro-tein kinase B). In prostate and ovarian cancer, upregulation of endothelin synthesis and ETA receptors has been associated with a progression of the disease. The inhibiton of ETA receptors results in a reduced tumour growth. In malignant melanoma, ETB receptors are associated with tumour progression. Endothelins can also stimulate apoptosis in stretch-activated vessels via the ETB receptor, which contrasts the above-mentioned effects. The molecular basis for these differential anti- and pro-apoptotic reactions mediated by endothelins remains elusive. 

GPI anchoring is a posttranslational modification occurring in the endoplasmic reticulum where preassembled GPI anchor precursors are transferred to proteins bearing a C-terminal GPI signal sequence. The GPI anchor precursors are synthesized in the endoplasmic reticulum by sequential addition of sugar and other components to phosphatidylinositol. Protein GPI anchors are ubiquitous in eukaryotic cells. In mammalian cells, GPI anchored proteins are often found in lipid rafts which are subdomains of the plasma membrane, containing various signaling components. 

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. 

Figure 1. Simplified schematic of receptor-mediated signal transduction in neutrophils. Binding of ligand to the receptor activates a guanine-nucleotide-binding protein (G protein), which then stimulates phospholipase C. Phosphatidylinositol 4,5-bis-phosphate is cleaved to produce diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG stimulates protein kinase C. IP3 causes the release of Ca from intracellular stores, which results in an increase in the cytosolic Ca concentration. This increase in Ca may stimulate protein kinase C, calmodulin-dependent protein kinases, and phospholipase A2. Protein phosphorylation events are thought to be important in stimulating degranulation and oxidant production. In addition, ionic fluxes occur across the plasma membrane. It is possible that phospholipase A2 and ionic channels may be governed by G protein interactions. ...

The inositol is present in ph osphatidylinositol as the stereoisomer, myoinositol (Figure 14—8). Phosphatidylinositol 4,5-hisphosphate is an important constituent of cell membrane phosphohpids upon stimulation by a suitable hormone agonist, it is cleaved into diacylglycerol and inositol trisphosphate, both of which act as internal signals or second messengers. 

Number of papers to date have shown that the CXCR4 receptors expressed in both neuronal and glial cells are functional and coupled to multiple intracellular pathways (Lazarini et al. 2003). The CXCR4 through pertussis toxin (PTX)- sensitive G proteins is coupled to at least two distinct signaling pathways (1) the first pathway, involving the activation of phosphatidylinositol- 3 (PI-3) kinase and extracellular signal... 

The major 3 -phosphoinositide products of class I PI3Ks are phosphati-dylinositol 3,4,5-trisphosphate [PI(3,4,5)P3, which is formed primarily from phosphorylation of PI(4,5)P2) and its metabolite phosphatidylinositol 3,4-bisphosphate, PI(3,4)P2]. The basal levels of PI(3,4)P2 and PI(3,4,5)P3 in cells are usually in low abundance but can rise sharply after cell stimulation to interact with an array of protein effectors via pleckstrin homology (PH) domains, modular segments of about 100 amino acids found in many signaling proteins. It is these PH-domain-containing proteins that are able to propagate and drive downstream signaling events. 

Knall C, Worthen GS, Johnson GL. Interleukin 8-stimulated phosphatidylinositol-3-kinase activity regulates the migration of human neutrophils independent of extracellular signal-regulated kinase and p38 mitogen-activated protein kinases. Proc Natl Acad Sci U S A 1997 94(7) 3052-3057. 

Sulpice E, Bryckaert M, Lacour J, Confreres JO, Tobelem G. Platelet factor 4 inhibits FGF2-induced endothelial cell proliferation via the extracellular signal-regulated kinase pathway but not by the phosphatidylinositol 3-kinase pathway. Blood 2002 100(9) 3087-3094. 

---