Phosphatidyl inositol phosphate-activated

Phosphatidyl-inositol phosphate and P1P2 showed significant increases in carbofuran-trcaied hepatocytes in comparison to DMSO-treated control. Equimolar amounts of carbofuran or BNF used in the separate culture. significantly increased the hepatocyte membrane PKC activity compared to the control. Use of staurosporinc, a known inhibitor of PKC, counteracted the carbofuran- or BNF-induced increase in PKC activity. Interestingly, phorbol ester demonstrated an attenuation of the carbofuran- or BNF-induced increase in PKC activity, but it remained higher than the control value. 

Krauss, M., Kinuta, M., Wenk, M. R., De Camilli, P., Takei, K., and Haucke, V. (2003). ARF6 stimulates clathrin/AP-2 recruitment to synaptic membranes by activating phosphatidyl-inositol phosphate kinase type Igamma. J. Cell. Biol. 162, 113-124. 

The other activity associated with transmembrane receptors is phospholipase C. Phosphatidyl inositol is a membrane phospholipid that after phosphorylation on the head group is found in the membrane as a phos-photidylinostitol bis phosphate. Phospholipase C cleaves this into a membrane associated diacylglycerol (the lipid part) and inositol trisphosphate (IP3, the soluble part). Both play a later role in elevating the level of the second messenger, Ca2+. 

Phosphatidyl-inositol-3-OH kinase (PI(3)kinase) plays an important role in the fusion of endosomes. Phosphatidyl-inositol-3-phosphate (PI(3)P), a product of this enzyme, is enriched in early endosomes, and blocking PI(3)kinase activity with the small molecule wortmannin prevents endosome fusion. This fungal natural product has been shown to inhibit the endocytosis of transferrin, horseradish peroxidase, and albumin (44, 45). 

Likewise, phosphatidyl inositol is formed by the transfer of a diacylglycerol phosphate unit from CDP-diacylglycerol to inositol. Subsequent phosphorylations catalyzed by specific kinases lead to the synthesis of phosphatidyl inositol 4,5-bisphosphate, an important molecule in signal transduction. Recall that hormonal and sensory stimuli activate phospholipase C, an enzyme that hydrolyzes this phospholipid to form two intracellular messengers—diacylglycerol and inositol 1,4,5-trisphosphate (Section 15.2). 

Cdt is related to a eukaryotic cytosolic enzyme, phosphatidyl inositol-3,4,5, triphosphate 5-phosphatase which removes the 5-phosphate group from phosphatidyl inositol-3,4,5, triphosphate. This activity is part of an intracellular signaling cascade induced by a ligand binding to a nearby receptor. Phosphatidyl inositol-3,4,5-triphosphate 5-phosphatase possesses an Src Homology 2 (SH2) domain in addition to its Inositol Phosphatase activity (SHIP). 

Phosphatidyl inositol, which is present in the inner leaflet of the plasma membrane, is convated to PM,5-bisP by kinases that phosphorylate the inositol ring at the 4 and 5 positions (Fig. 11.12). PM,5-bisP, which has three phosphate groups, is cleaved by a phospholipase C-isozyme to generate IP3 and DAG. The phospholipase isozyme C., (PLC.,) is activated by tyrosine kinase growth factor receptors, and phospholipase C 3 is activated by a heptahelical receptor-G protein signal ffansduction pathway. 

Certain heptahelical receptors bind the q isoform of the Ga subunit (Ga ), which activates the target enzyme phospholipase Cp (see Fig. 11.12). When activated, phospholipase Cp hydrolyzes the membrane lipid phosphatidyl inositol bis phosphate (PI-4,5-bisP) into two second messengers, diacylglycerol (DAG) and... 

Fig. 15 Intracellular phosphatidyl inositol metabolism and postulated roles for inositol phosphates as secondary messengers (adapted from Housley, 1987). (1) One or more of the inositol phosphates (including I(1,4,5)P3) stimulates rapid release of calcium from intracellular stores. (2) Feedback from initial rapid calcium release stimulates intracellular inositol phosphate metabolism. (3) Secondary increase in intracellular calcium levels through activation of membrane calcium-gates and influx of extracellular calcium stimulated by inositol phosphates. PC = phospholipase C.

Figure 50. PTEN. The tumor suppressor gene and gene product protein PTEN (phosphatase tensin homolog deleted on chromosome ten, human 10q23.3) (Table VIII), is the natural inhibitor of oncogenes PI3K/Akt (phosphatidyl inositol kinase 3 protein kinase 3 phosphatidylinositol 3 phosphate Jacob Furth s AK mouse strain thymic lymphoma retroviral oncogene phosphoinosite-dependent kinase). The PTEN protein inactivates PIP3 by dephosphorylation PDKl (phosphoinositol-dependent kinase) is not recruited to the plasma membrane to activate Akt by phosphorylation. Sarah M. Planchon et al. The nuclear affairs of PTEN. J Cell Sci 2008 121 249-253. doi 10.1242/jcs.022459...

Inositol phosphates phosphate esters of the cyclic alcohol myo-inositol. They are found in the plasma membrane as components of phospholipids known as phosphatidyl inositols. Inositol 1,4,5-truphosphate (InsP]) is released from phosphatidylinositol-43-hplasma membrane by a variety of membrane receptors for hormones or neu-rotransmitters when the receptors are occupied. InsPj appears to be the active species responsible for the release of Ca which follows stimulation of the cell it is thus a second messenger (see Hormones, Caldum) for such agents as acetylcholine, vasopressin, substance P and epidermal growth factor (see Peptide hormones). 

Phosphatidyl inositol-3 phosphate hapten (PI3P) (138) has been synthesised in a seven step procedure and then conjugated to the maleimide-activated keyhole limpet hemocyanin (KLH) to provide a PI3P immunogen (139). Biochemically validation showed that the immunogen (139) could be successfully used to generate selective PI3P antibodies. ... 

S ATP -I- 1-phosphatidyl-1 D-myo-inositol 3-phosphate <1, 2> (<1>, stress-activated enzyme [1] <1>, essential for vacuole function [1] <1>, generation of 1-phosphatidyl-1 D-myo-inositol 3,5-hisphosphate is regulated... 

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