Rapid breakdown of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in rat hepatocytes stimulated by vasopressin and other Ca2+-mobilizing hormones

Creba, Judith A.; Downes, C P; Hawkins, Phillip T.; Brewster, Glenna; Michell, Robert H.; Kirk, C J

doi:10.1042/bj2120733

Cited by 541 publications

(234 citation statements)

References 92 publications

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“…This is of particular relevance since cellular levels of inositol lipids respond quickly to a range of extracellular agonists. For example, levels of PtdIns(4,5)P 2 have been known for many years to fall by up to 50% during the initial few seconds of receptor-dependent activation of phospholipase C (28). Such an effect is very transient, and lipid levels typically return to near-stimulated levels within 1-2 min.…”

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confidence: 99%

Regulation of AP-3 Function by Inositides

Hao

Tan

Prasad

et al. 1997

Journal of Biological Chemistry

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As part of the growing effort to understand the role inositol phosphates and inositol lipids play in the regulation of vesicle traffic within nerve terminals, we determined whether or not the synapse-specific clathrin assembly protein AP-3 can interact with inositol lipids. We found that soluble dioctanoyl-phosphatidylinositol 3,4,5-trisphosphate (DiC 8 PtdIns(3,4,5)P 3 ) was only 7.5-fold weaker a ligand than D-myo-inositol hexakisphosphate in assays that measured the displacement of D-myo-[3 H]inositol hexakisphosphate. In functional assays we found that both of these ligands inhibited clathrin assembly, but DiC 8 -PtdIns(3,4,5)P 3 was more potent and exhibited a larger maximal effect. We also examined the structural features of DiC 8 -PtdIns(3,4,5)P 3 that establish specificity. Dioctanoyl-phosphatidylinositol 3,4-bisphosphate, which does not have a 5-phosphate, and 4,5-O-bisphosphoryl-D-myo-inosityl 1-O-(1,2-O-diundecyl)-sn-3-glycerylphosphate, which does not have a 3-phosphate, were, respectively, 2-fold and 4-fold less potent than DiC 8 -PtdIns(3,4,5)P 3 as inhibitors of clathrin assembly. Deacylation of DiC 8 -PtdIns(3,4,5)P 3 reduced its affinity for AP-3 almost 20-fold, and also dramatically lowered its ability to inhibit clathrin assembly. The deacylated products of the soluble derivatives of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate were both not significant inhibitors of clathrin assembly. It therefore appears that the interactions of inositides with AP-3 should not be considered simply in terms of electrostatic effects of the highly charged phosphate groups. Ligand specificity appears also to be mediated by hydrophobic interactions with the fatty-acyl chains of the inositol lipids.There is increasing evidence that certain inositides (members of a large family of inositol phosphates and inositol lipids) act at several levels to regulate both the recruitment and the activation of proteins involved in vesicular transport. PtdIns(3,4,5)P 3 , 1 and the polyphosphoinositide 3-kinase that synthesizes this lipid both feature prominently in this area (1, 2). For example, intracellular trafficking of tyrosine kinase receptors depends upon interactions between the internalized receptors and the 3-kinase (3). Additionally, PtdIns(3,4,5)P 3 interacts either directly or indirectly with several GTPases that play important roles in vesicle traffic (1). Finally, in yeast, the Vps34 protein that is essential for Golgi to vacuole transport is a phosphoinositide 3-kinase (4).Interest in this field is not restricted to the inositol lipids. Other studies into the roles of the inositides in protein traffic have ascertained that certain inositol polyphosphates can bind with high affinity to the clathrin assembly proteins, AP-2 and AP-3 (5-9). AP-2 is believed to play a general role in endocytosis, since it has been found on vesicles budding from the plasma membranes of all types of cells (10). AP-3 is believed to play a more specialized role in synaptic vesicle biogenesis and recycling...

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confidence: 99%

Regulation of AP-3 Function by Inositides

Hao

Tan

Prasad

et al. 1997

Journal of Biological Chemistry

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“…The elution of protein by a linear NaCl gradient was followed at 280 nm (----). Enzyme activities were determined using 15 pl of column eluate and an incubation time of 5 …”

Section: Resultsmentioning

confidence: 99%

Phosphatidylinositol-4-phosphate kinase from rat brain. Activation by polyamines and inhibition by phosphatidylinositol 4,5-bisphosphate

1986

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Phosphatidylinositol-4-phosphate (PtdIns-P) kinase was purified approximately 30-fold from rat brain cytosol. No contaminating activity of PtdIns kinase or of phosphomonoesterase and phospholipase C using PtdIns-P or PtdIns-P2 as substrate could be detected in the enzyme preparation. The PtdIns-P kinase activity was severalfold higher when PtdIns-PIPtdEtn vesicles rather than PtdIns-P alone were used as substrate. This might be due to increased accessibility of the enzyme for the vesicular substrate, further indicated by the lower activity obtained when PtdCho or PtdIns, phospholipids with bulky head groups, was also present in the vesicles. The product PtdIns-P2 was a competitive inhibitor with respect to PtdIns-P and 50% inhibition of enzyme activity was observed at the same product concentration regardless of whether the substrate-product mixture was presented in vesicular or micellar form, or the substrate and product were added in separate vesicles.The polyamines spermine and spennidine enhanced PtdIns-P kinase activity severalfold. Spermine also caused a shift in the MgClz saturation curve from sigmoidal to hyperbolic, lowering the MgZ + concentration required for optimum kinase activity to the physiological range. Myelin basic protein enhanced the enzyme activity when PtdIns-PIPtdEtn vesicles were used as substrate, whereas it was inhibitory when PtdIns-P was added alone. The possible role of polyamines and the product PtdIns-P2 in the regulation of PtdIns-P kinase activity is discussed.According to recent hypotheses, PtdIns-Pz constitutes the substrate for a receptor-controlled phospholipase C reaction which generates diacylglycerol and inositol trisphosphate. These products then act as intracellular messengers for the activation of a protein kinase (kinase C) and for the mobilization of intracellular CaZ+, respectively [I, 21. In addition, PtdIns-P2 in the plasma membrane might play other functional roles, such as in the regulation of actin polymerization [3].

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“…Deacylation was based on the method of Creba et al [16]. Anti-insulin IgG was prepared from guinea pig anti-insulin serum by ammonium sulfate precipitation and DEAE-cellulose column chromatography [17].…”

Section: Other Methodsmentioning

confidence: 99%

A significant increase of lysophosphatidylinositol 4‐phosphate with insulin in isolated rat fat cells

et al. 1987

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We studied the effects of insulin on the incorporation of 32P i into phospholipids in rat fat cells. When the cells were treated with insulin, a new radioactive phospholipid was detected on thin layer chromatography. The substance migrated slower than phosphatidylinositol 4,5-bisphosphate and was hardly detectable in the absence of insulin. This effect of insulin was both time-and dose-dependent with half-maximal stimulation at 120 #U/ml. Pretreatment of insulin with anti-insulin antibody or the cells with anti-insulin receptor antibody inhibited the effect of insulin. The product of phosphatidylinositol 4-phosphate hydrolyzed by phospholipase A z was coincided with the substance on thin layer chromatography. Quinacrine inhibited the formation of the substance in a dose-dependent manner. These results suggested that insulin stimulates the generation of lysophosphatidylinositol 4-phosphate through the insulin-receptor interaction.

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Rapid breakdown of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in rat hepatocytes stimulated by vasopressin and other Ca2+-mobilizing hormones

Cited by 541 publications

References 92 publications

Regulation of AP-3 Function by Inositides

Regulation of AP-3 Function by Inositides

Phosphatidylinositol-4-phosphate kinase from rat brain. Activation by polyamines and inhibition by phosphatidylinositol 4,5-bisphosphate

A significant increase of lysophosphatidylinositol 4‐phosphate with insulin in isolated rat fat cells

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