The diphosphoinositide kinase of rat brain

Kai, Masahiro; Salway, J. G.; Hawthorne, J. N.

doi:10.1042/bj1060791

Cited by 128 publications

(42 citation statements)

References 22 publications

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“…This product may be further phosphorylated via PIP kinase and ATP to form phosphatidylinositol 4,5-bisphosphate (PIP2) (Kai et al, 1968). It had been shown by Hokin and Hokin (1 955), in studies in which intact cell preparations were incubated in the presence of muscarinic ligands, that the labeling of two quantitatively minor lipids, phosphatidate (PA) and PI, was enhanced.…”

Section: Chemistry and Enzymology Of Inositol Lipids And Inositol Phomentioning

confidence: 99%

“…The standard IUPAC-IUB abbreviations for phosphatidylinositol, phosphatidylinositol4-phosphate, arid phosphatidylinositol 4,s-bisphosphate are PtdIns, PtdIns 4-P, and Pt- ence of a transferase (Benjamins and Agranoff, 1969) and can then be phosphorylated via PI kinase and ATP to form phosphatidylinositol4-phosphate (PIP) (Colodzin and Kennedy, 1965;Kai et al, 1966). This product may be further phosphorylated via PIP kinase and ATP to form phosphatidylinositol 4,5-bisphosphate (PIP2) (Kai et al, 1968). It had been shown by Hokin and Hokin (1 955), in studies in which intact cell preparations were incubated in the presence of muscarinic ligands, that the labeling of two quantitatively minor lipids, phosphatidate (PA) and PI, was enhanced.…”

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Receptor Activation and Inositol Lipid Hydrolysis in Neural Tissues

Fisher

Agranoff

1987

Journal of Neurochemistry

331

109

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Recent advances in our knowledge of the biochemistry, pharmacology, and cell biology of ligand-induced, stimulated turnover of inositol lipids in such diverse tissues as insect salivary glands, platelets, lymphocytes, and a number of exocrine glands have greatly altered our understanding of intracellular events leading to secretion, contraction, chemotaxis, and other cellular responses. Much of what has been learned regarding ligand-stimulated turnover of inosito1 lipids has come from nonneural systems, so that the presumption that signal transduction via this mechanism mediates significant steps in neural function must still be considered inferential. This reservation has been a major theme of a recent comprehensive review (Hawthorne, 1986). Nevertheless, that the brain contains large amounts of the substrates and enzymes of inositol lipid turnover and its associated second messenger systems and, further, that it is enriched with receptors that are linked to stimulated inositol lipid turnover argue strongly that the phosphoinositides indeed play an important role in brain function. There exist several general reviews on stimulated inositol lipid turnover (Bemidge, 1984;Bemdge and Irvine, 1984;Nishizuka, 1984Nishizuka, , 1986Hokin, 1985;Abdel-Latif, 1986;Downes, 1986;Williamson, 1986), including several that emphasize the nervous system (Downes, 1982(Downes, , 1983Fisher and Agranoff, 1986;Hawthorne, 1986; Nahorski et al., 1986). The present contribution emphasizes developments of neurochemical relevance since a review on the subject in this journal 8 years ago (Hawthorne and Pickard, 1979). CHEMISTRY AND ENZYMOLOGY OF INOSITOL LIPIDS AND INOSITOL PHOSPHATESThe inositol lipids Phosphatidylinositol (PI), depicted in Fig. lA, is a glycerophospholipid in which the sn-1 and sn-2 positions of glycerol are esterified to fatty acids, whereas the sn-3 position is phosphodiesterified to the 1)-1 position of myo-inositol. myo-Inositol is one of nine possible isomers of hexahydroxycyclohexane, which, in its preferred chair conformation, has one axial and five equatorial hydroxyl groups. The molecule can be likened to a turtle (Fig. 1B) in which the four legs and tail are the five equatorial hydroxyls, numbered counterclockwise from above, starting with the right foreleg as position D-1 (Fig. 1 C). The turtle's head is thus the axial hydroxyl at position D-2. The phosplhatidyl group in all of the phosphoinositides is linked to D-1 (the right foreleg).PI is synthesized in brain from a liponucleoiide intermediate, cytidine diphosphodiacylglycerol (CDP-DG) (Agranoff et al., 1958), and inositol in the presAddress correspondence and reprint requests to Dr. B. W. Agranoff at Neuroscience Laboratory Building, University of Michigan, 1103 East Huron, Ann Arbor, MI 48104-1687, U.S.A.Abbreviations used: ACh, acetylcholine; ACTH, corticotropin ( I-24)tetracosapeptide; APB, ~~-2-amino-4-phosphobutyric acid; APV, DL-2-amino-5-phosphonovalerate; CDP-DG, cytidine diphosphodiacylglycerol; DG, 1,2-diacyl-sn-glycerol; GAP, growthassociated ...

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Section: Chemistry and Enzymology Of Inositol Lipids And Inositol Phomentioning

confidence: 99%

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confidence: 99%

Receptor Activation and Inositol Lipid Hydrolysis in Neural Tissues

Fisher

Agranoff

1987

Journal of Neurochemistry

331

109

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“…PIP2 is formed from PI through stepwise phosphorylation by PI kinase (EC 2.7.1.67) and PIP kinase (EC 2.7.1.68). These kinases are known to exist in a variety of tissues (7,8,15,17,(20)(21)(22)30). There are also corresponding phosphomonoesterases (23,33,36), and the inositol lipids mentioned above are thought to be in equilibrium with each other through "futile cycles" constituted by these kinases and esterases.…”

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Phosphatidylinositol kinase activity in virus-transformed and nontransformed cells.

Sugano¹,

Hanafusa²

1985

Mol. Cell. Biol.

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We assayed phosphatidylinositol (PI) kinase (EC 2.7.1.67) activity in detergent extracts of nontransformed or virus-transformed cells. Nontransformed chicken embryo fibroblasts (CEF) contain PI kinase activity with an apparent specific activity of 20 pmol/min per mg of protein. This activity sedimented as a single peak with a molecular weight of approximately 60,000 in a glycerol gradient, although immunoprecipitation with anti-p60src sera showed that the PI kinase activity is distinct from p60c-src. Extracts from CEF transformed by Rous sarcoma virus, Fujinami sarcoma virus, or avian sarcoma virus UR2 showed no elevation of PI kinase activity over nontransformed CEF. Removal of the oncogene products from extracts by immunoprecipitation did not change the level of PI kinase activity in extracts, suggesting that putative virus-coded PI kinases do not make a significant contribution to overall levels of PI kinase activity in transformed cells. Additionally, P140Wagf-Is was separated from cellular PI kinase by phosphocellulose chromatography. This partially purified fraction contained low PI kinase activity distinct from Pl40W-fPs; indicating that p140Wzg.-fiS has no detectable PI kinase activity.There has been a great deal of interest in an intracellular signaling system that utilizes inositol lipids and might be involved in regulating cell growth (1,26,29,32). Various stimuli induce the rapid hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) by phospholipase C to diacylglycerol and inositol trisphosphate which act as second messengers. Diacylglycerol activates protein kinase C, and inositol trisphosphate mobilizes intracellular calcium. This hydrolysis is followed by the phosphorylation of phosphatidylinositol (PI) and phosphatidylinositol-4-monophosphate (PIP). PIP2 is formed from PI through stepwise phosphorylation by PI kinase (EC 2.7.1.67) and PIP kinase (EC 2.7.1.68). These kinases are known to exist in a variety of tissues (7,8,15,17,(20)(21)(22)30). There are also corresponding phosphomonoesterases (23,33,36), and the inositol lipids mentioned above are thought to be in equilibrium with each other through "futile cycles" constituted by these kinases and esterases. The close relation between this signaling system and cell growth regulation was suggested by the fact that several growth factors could induce PI turnover (10,14,34). In addition, tumor-promoting phorbol esters can stimulate protein kinase C directly (5).The stimulation of this system in the transforming process of a tumor virus was first suggested by Diringer and Friis (9) PI. They suggested that various oncogene products possessing tyrosine kinase activity might also have PI kinase activity and that PI kinase activity is responsible for transformation.In this report, we asked two questions relevant to two important points of the above hypotheses. (i) If elevated PI turnover is a direct effect of the PI kinase activity of oncogene products, then what is the difference in the overall PI kinase activity between transformed and nontransfor...

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“…For this reason they are better candidates for a response linked to cell-surface receptors than PtdIns, which occurs in most of the membranes of the cell. They are also particularly labile, a point that was made when the kinase-forming PtdIns(q,5)P2 was first described (Kai et al 1968), the relative rates of synthesis and hydrolysis being compared with those for acetylcholine. Because of this it was suggested by Kai et al (1968) that PtdIns(q,s)P, had properties reminiscent of a chemical transmitter which was rapidly destroyed after receptor activation.…”

Section: Receptor-linked Metabolism Of Ptdins or Polyphosphoinositides?mentioning

confidence: 99%

Inositol phospholipid and phosphatidic acid metabolism in response to membrane receptor activation

Hawthorne¹

1985

Proc. Nutr. Soc.

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The status of myo-inositol ( Fig. r(a)) as a vitamin is uncertain since some human tissues can synthesize it from glucose-6-phosphate. Eagle et a1. (1957), however, showed that it was an essential growth factor for many human cells in tissue culture. The concentration required for optimum growth was higher than would be expected of a typical vitamin, suggesting a metabolic role for inositol. It now seems clear that this role involves the phospholipids which contain inositol, phosphatidylinositol (PtdIns), phosphatidylinositol-4-phosphate (PtdInsqP; Fig. ~( b ) )and phosphatidylinositol-q,5-bisphosphate (PtdIns(,+,g)P,; Fig. ~( c ) ) . For the nutritionist these phosphoinositides are of interest in at least three ways. First, their metabolism is linked to activation of many cell-surface receptors, most of which mobilize calcium (Michell, 1975). Second, very recent studies connect the phosphoinositides with control of cell proliferation through epidermal growth factor and with malignant transformation of cells. Third, these lipids are rich in arachidonic acid and in some cells this particular pool of the acid is used as a source of prostanoids. The present paper concentrates on the first two of these topics since they are attracting a good deal of attention and some controversy. Phosphoinositides and

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The diphosphoinositide kinase of rat brain

Cited by 128 publications

References 22 publications

Receptor Activation and Inositol Lipid Hydrolysis in Neural Tissues

Receptor Activation and Inositol Lipid Hydrolysis in Neural Tissues

Phosphatidylinositol kinase activity in virus-transformed and nontransformed cells.

Inositol phospholipid and phosphatidic acid metabolism in response to membrane receptor activation

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