Phosphatidylinositol phosphate-activated

Davis, A.J., Perera, I.Y., and Boss, W.F., 2004, Cyclodextrins enhance recombinant phosphatidylinositol phosphate kinase activity. J. Lipid. Res. 45 1783-1789. 

Kunz, J., Wilson, M.P., Kisseleva, M., Hurley, J.H., Majerus, P.W., and Anderson, R.A., 2000, The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity. 

Fig. 11.13. Insulin receptor signaling. The insulin receptor is a dimer of two membrane-spanning a-(3 pairs. The tyrosine kinase domains are shown in blue, and arrows indicate auto-crossphosphorylation. The activated receptor binds IRS molecules (insulin receptor substrates) and phos-phorylates IRS at multiple sites, thereby forming binding sites for proteins with SH2 domains Grb2, phospholipase C"y(PLC"y), and PI 3-kinase. These proteins are associated with various phosphatidylinositol phosphates (all designated with PIP) in the plasma membrane.

Matsui, T., Yonemura, S., Tsuldta, S. and Tsukita, S. (1999). Activation of ERM proteins in vioo by Rho involves phosphatidylinositol -phosphate 5-kinase and not ROCK kinases. Curr. Biol. 9, 1259—1262. 

Fig. 9. Speculative scenario of nutrient y-linolenic acid (GLA)/linoleic acid (LA) modulation of nuclear transcription factor. Abbreviations 15-LOX, 15-lipoxygenase 15S-HETrE, 15S-hydroxyeicosatrienoic acid 13-HODE, 13-hydroxyoctadecadienoic PIP, phosphatidylinositol phosphate PKC, protein kinase C DAG, diacylglycerol MAPK, mitogen-activated protein kinase AP-1, activator protein 1.

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 phosphatidylinositol phosphate kinase type Ig. J. Cell Biol 162, 113-124. 

Schaletzky, J, Dove, SK, Short, B, Lorenzo, O, Clague, MJ and Barr, FA (2003) Phosphatidylinositol-5-phosphate activation and conserved substrate specificity of the myotubularin phosphatidylinositol 3-phosphatases. Curr Biol, 13, 504-509. 

Family of enzymes phosphorylating phosphatidylinositol (Ptdlns), PtdIns(4)phosphate, and PtdIns(4,5)phosphate in the 3-position. The Ptdlns(3 phospholipids are second messengers in processes like cell growth, cytoskeletal rearrangement, and vesicular transport. PI 3-kinases are heterodimers composed of a catalytic and a regulatory subunit. The enzymes are activated by insulin, many growth factors, and by a variety of cytokines. Their activity can be inhibited by wortmannin and LY294002. 

P2 is generated from PtdIns(4)P by the enzymatic activity of phosphatidylinositol 4-phosphate 5-kinase (PDP5K) (Fig. 1). Additional pathways are likely to be discovered. 

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. ...

More recently, the importance of a group of highly polar inositol lipids, present in neutrophils and many other cell types, has been recognised. Activation of neutrophils by fMet-Leu-Phe results in the transient accumulation of phosphatidylinositol 3-phosphate (Ptdlns 3-P), phosphatidylinositol 3,4-bisphosphate (Ptdlns 3,4-P2) and phosphatidylinositol 3,4,5-trisphosphate (Ptdlns 3,4,5-P3). Apparently, the enzyme phosphatidylinositol 3-hydroxy (3-OH) kinase plays a key role in the formation of these novel lipids. This enzyme can catalyse the formation of these lipids from phosphatidylinositol, phosphatidylinositol 4-phosphate (Ptdlns 4-P) and phosphatidylinositol 4,5 bisphosphate (Ptdlns 4,5-P2) in vitro (Fig. 6.10). Alternatively, it is possible that Ptdlns 3,4-P2 and Ptdlns 3-P are derived from the sequential dephosphorylation of Ptdlns 3,4,5-P3. 

The binding of the sperm to a receptor on the membrane of the oocyte either activates a membrane-bound phospholipase or releases a phospholipase into the oocyte. The phospholipase hydrolyses phosphatidylinositol bisphos-phate to produce the two intracellular signals, inositol tris-phosphate (IP3) and diacylglycerol within the ovum. As in other cells, the IP3 signal increases the level of cytosolic Ca + ions and the diacylglycerol (DAG) signal activates protein kinase C. 

The same basic biochemical control mechanism causes contraction of the smooth muscle as well as secretion of aldosterone. The binding of angiotensin to its receptor activates a membrane phospholipase-C. It catalyses the hydrolysis of phosphoinositide phosphatidylinositol bis-phosphate to produce the two intracellular messengers, inositol trisphosphate (IP3) and diacylglycerol (DAG). 

FIPhosphatidylinositol cycle. A = activator CMPPA = cytidine monophosphate phosphatidic acid DAG = diacylglycerol G = G protein Glu-6-P, glucose 6-phosphate IPj = inositol monophosphate IP2 = inositol biphosphate ... 

Fig. 3. A simplified illustration of BCR-ABL and SRC family kinase involvement in oncogenic signaling pathways. The inhibitory effect is indicated by the upside-down T s. ABL = Abelson tyrosine kinase BCR = breakpoint cluster region FAK = focal adhesion kinase Grb-2 = growth factor receptor-bound protein 2 HcK = hematopoietic cell kinase JNK = Jun amino-terminal kinase P = phosphate group PI3 K = phosphatidylinositol-3-kinase SFK = SRC family kinases StatS = signal transducer and activator of transcription 5. (Reprinted with permission from Ref (123)). 

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