Phosphatidylinositol 4-phosphate

The FYVE domain is a phosphatidylinositol-3-phosphate-binding module of approximately 60 to 80 amino acids. It was named after the first four proteins, where this domain was described (Fablp, YOTB, Vaclp and EEA1). 

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. 

Misra, S. and J. H. Hurley, Crystal structure of a phosphatidylinositol 3-phosphate-specific membranetargeting motif, the FYVE domain of Vps27p. Cell, 1999, 97(5), 657-66. 

Blondeau, E Laporte, J. Bodin, S. Superti-Furga, G. Payrastre, B. Man-del, J.-L. Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway. Hum. Mol. Genet., 9, 2223-2229 (2000)... 

Cooke, F.T. Dove, S.K. McEwen, R.K. Painter, G. Holmes, A.B. Hall, M.N. Michell, R.H. Parker, P.J. The stress-activated phosphatidylinositol 3-phosphate 5-kinase Fablp is essential for vacuole function in S. cerevisiae. Curr. Biol., 8, 1219-1222 (1998)... 

Gary, J.D. Sato, T.K. Stefan, C.J. Bonangelino, C.J. Weisman, L.S. Emr, S.D. Regulation of fabl phosphatidylinositol 3-phosphate 5-kinase pathway by vac7 protein and fig4, a polyphosphoinositide phosphatase family member. Mol. Biol. Cell, 13, 1238-1251 (2002)... 

Morishita, M. Morimoto, E Kitamura, K. Koga, T Fukui, Y. Maekawa, H. Yamashita, I. Shimoda, C. Phosphatidylinositol 3-phosphate 5-kinase is required for the cellular response to nutritional starvation and mating pheromone signals in Schizosaccharomyces pombe. Genes Cells, 7, 199-215 (2002)... 

Phosphorylated IRS-1 activates a second signaling pathway by interacting with an 85-kDa SH2-containing protein that is a subunit of phophatidylinositol 3-kinase.384 386 This activates the 110-kDa catalytic subunit of the 3-kinase, which catalyzes formation of phosphatidylinositol 3-phosphate as well as Ptdlns (3,4)P2 and Ptdlns (3,4,5)P3.387/387a These compounds, which remain within membranes, activate other branches of the signaling cascade, some of which may converge with those of the MAP kinase cascade. However, there appears to be specific activation of a ribosomal Ser/Thr kinase that, among other activities, phosphorylates ribosomal protein S6, a component of the small ribosomal subunit.388 It also phosphorylates some isoforms of protein kinase C and other enzymes. Ptdlns 3-kinase may also activate 6-phosphofructo-2-kinase (Fig. 11-2, step ti).384/388... 

Fig. 1. Schematic representations of D-phosphatidylinositol 3-phosphate [PtdIns(3)P], D-phosphatidylinositol 3,4-bisphosphate [PtdIns(3,4)P2] and D-phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3].

Whitman, M Downes, C. P Keeler, M Keller, T and Cantley, L. (1988) Type 1 phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol 3-phosphate. Nature 33, 644-646. 

Walsh, J. P., Caldwell, K. K., and Majerus, P. W. (1991) Formation of phosphatidylinositol 3-phosphate by isomerisation from phosphatidylinositol 4-phosphate. Proc. Natl. Acad. Sci. USA 88, 9184-9187. 

Munnik, T., Irvine, R.F. and Musgrave, A., 1994, Rapid turnover of phosphatidylinositol 3-phosphate in the green alga Chlamydomonas eugametos signs of a phosphatidylinositide 3-kinase signaling pathway in lower plants Biochem. J. 298 269-273. 

Taylor, G.S., Maehama, T., and Dixon, J.E., 2000, Inaugural article Myotubularin, a protein tyrosine phosphatase mutated in myotubular myopathy, dephosphorylates the lipid second messenger, phosphatidylinositol 3-phosphate. Proc. Natl. Acad. Sci. U. S. A. 97 8910-8915. 

Phosphatidylinositol 3-phosphate (PI-3-P, 2) is a rare phospho-fipid generated from PI by the action of Class II and Class in PI-3 kinase (PI-3K) (30, 31) and via hydrolysis of the 5-phosphate from PI-3,5-P2 by phosphatidylinositol phosphate 5-phosphatases SHIP (32). 

As in the case of sstl, agonist binding to sst4 has and has not been shown to be sensitive to GTP and PTX similarly, inhibition of AC was and was not observed (Demchyshyn et al. 1993 Raynor et al. 1993a Kaupmann et al. 1994 Roosterman et al. 1997). In transfected cells, sst4 was functionally coupled, in a PTX-sensitive fashion, not only to inhibition of AC, but also to activation of arachidonate release and mitogen-activated protein kinase cascade (Bito et al. 1994 Shimizu et al. 1996). These effects were accompanied by the phosphorylation of 85-kDa cytosolic phospholipase A2 and were inhibited by the phosphatidylinositol-3-phosphate kinase inhibitor wortmannin. 

A FIGURE 14-26 Generation of phosphatidylinositol 3-phosphates. The enzyme phosphatidylinositol-3 kinase (PI-3 kinase) is recruited to the membrane by many activated receptor tyrosine kinases (RTKs) and cytokine receptors. The 3-phosphate added by this enzyme is a binding site for various signal-transduction proteins. [See L. Rameh and L. C. Cantley, 1999, J. Biol. Chem. 274 8347]... 

Fig. 21.2 Negative ion MALDI-TOF mass spectra of l-palmitoyl-2-oleoyl-sn-phosphatidyl-ethanolamine (a), l-palmitoyl-2-oleoyl-sn-phosphatidylserine (b) and 1,2-dipalmitoyl-sn-phosphatidylinositol-3-phosphate (c). In all cases a 0.5 M solution of DHB in methanol was used as matrix and the sample solutions (0.5 mg/ml) diluted 1 1 (v/v) with the matrix. All peaks are marked according to their m/z ratio and DHB matrix peaks are marked with asterisks. Please note the considerable intensity of the cluster ions between DHB and the different analytes. Please also note that the contribution of matrix peaks is much higher than in the positive ion spectra...

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...

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