Pathophysiological concentrations of amyloid β proteins directly inhibit rat brain and recombinant human type II phosphatidylinositol 4-kinase activity

2004 ◽  
Vol 91 (5) ◽  
pp. 1164-1170 ◽  
Author(s):  
Bo Wu ◽  
Kaori Kitagawa ◽  
Nan-Yan Zhang ◽  
Bing Liu ◽  
Chiyoko Inagaki
Keyword(s):  
Rat Brain ◽  
Kinase Activity ◽  
Amyloid Β ◽  
Type Ii ◽  
Human Type ◽  
Phosphatidylinositol 4

Nuclear localization of phosphatidylinositol 4-kinase β

2002 ◽  
Vol 115 (8) ◽  
pp. 1769-1775 ◽  
Author(s):  
Petra de Graaf ◽  
Elsa E. Klapisz ◽  
Thomas K. F. Schulz ◽  
Alfons F. M. Cremers ◽  
Arie J. Verkleij ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Kinase Activity ◽  
Insoluble Fraction ◽  
Type Ii ◽  
3T3 Cells ◽  
Type Iii ◽  
Pore Complexes ◽  
Phosphatidylinositol 4 ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

Whereas most phosphatidylinositol 4-kinase (PtdIns 4-kinase) activity is localized in the cytoplasm, PtdIns 4-kinase activity has also been detected in membranedepleted nuclei of rat liver and mouse NIH 3T3 cells. Here we have characterized the PtdIns 4-kinase that is present in nuclei from NIH 3T3 cells. Both type II and type III PtdIns 4-kinase activity were observed in the detergent-insoluble fraction of NIH 3T3 cells. Dissection of this fraction into cytoplasmic actin filaments and nuclear lamina-pore complexes revealed that the actin filament fraction contains solely type II PtdIns 4-kinase,whereas lamina-pore complexes contain type III PtdIns 4-kinase activity. Using specific antibodies, the nuclear PtdIns 4-kinase was identified as PtdIns 4-kinase β. Inhibition of nuclear export by leptomycin B resulted in an accumulation of PtdIns 4-kinase β in the nucleus. These data demonstrate that PtdIns 4-kinase β is present in the nuclei of NIH 3T3 fibroblasts,suggesting a specific function for this kinase in nuclear processes.

scholarly journals A monoclonal antibody distinguishes two types of phosphatidylinositol 4-kinase

1991 ◽  
Vol 273 (1) ◽  
pp. 63-66 ◽  
Author(s):  
G C Endemann ◽  
A Graziani ◽  
L C Cantley
Keyword(s):  
Monoclonal Antibody ◽  
Rat Brain ◽  
Rat Liver ◽  
Bovine Brain ◽  
Human Erythrocytes ◽  
Gene Products ◽  
Type Ii ◽  
Type Iii ◽  
Distinct Gene ◽  
Phosphatidylinositol 4

A monoclonal antibody has been developed against the type II PtdIns 4-kinase from bovine brain. This antibody, 4C5G, causes greater than 90% inhibition of the type II PtdIns 4-kinase from bovine brain, rat brain and human erythrocytes. However, it fails to inhibit type III PtdIns 4-kinase from bovine brain or PtdIns 3-kinase from rat liver. These results suggest that type II and type III PtdIns 4-kinases are distinct gene products, and that 4C5G will be useful in studying the function of the type II PtdIns 4-kinase.

scholarly journals Phosphatidylinositol 4-kinase type II  is responsible for the phosphatidylinositol 4-kinase activity associated with synaptic vesicles

2003 ◽  
Vol 100 (7) ◽  
pp. 3995-4000 ◽  
Author(s):  
J. Guo ◽  
M. R. Wenk ◽  
L. Pellegrini ◽  
F. Onofri ◽  
F. Benfenati ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Kinase Activity ◽  
Type Ii ◽  
Phosphatidylinositol 4

Attenuation of amyloid β (Aβ)-induced inhibition of phosphatidylinositol 4-kinase activity by Aβ fragments, Aβ20–29 and Aβ31–35

2006 ◽  
Vol 396 (2) ◽  
pp. 148-152 ◽  
Author(s):  
Bo Wu ◽  
Kaori Kitagawa ◽  
Bing Liu ◽  
Nan-Yang Zhang ◽  
Zheng-Mei Xiong ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Amyloid Β ◽  
Phosphatidylinositol 4

scholarly journals Phosphatidylinositol-4-Kinase Type II Alpha Contains an AP-3–sorting Motif and a Kinase Domain That Are Both Required for Endosome Traffic

2008 ◽  
Vol 19 (4) ◽  
pp. 1415-1426 ◽  
Author(s):  
Branch Craige ◽  
Gloria Salazar ◽  
Victor Faundez
Keyword(s):  
Synaptic Vesicles ◽  
Kinase Activity ◽  
Kinase Domain ◽  
Membrane Domains ◽  
Type Ii ◽  
Catalytic Domains ◽  
Sorting Motif ◽  
Lysosome Related Organelles ◽  
Mutant Phenotypes ◽  
Phosphatidylinositol 4

The adaptor complex 3 (AP-3) targets membrane proteins from endosomes to lysosomes, lysosome-related organelles and synaptic vesicles. Phosphatidylinositol-4-kinase type II α (PI4KIIα) is one of several proteins possessing catalytic domains that regulate AP-3–dependent sorting. Here we present evidence that PI4KIIα uniquely behaves both as a membrane protein cargo as well as an enzymatic regulator of adaptor function. In fact, AP-3 and PI4KIIα form a complex that requires a dileucine-sorting motif present in PI4KIIα. Mutagenesis of either the PI4KIIα-sorting motif or its kinase-active site indicates that both are necessary to interact with AP-3 and properly localize PI4KIIα to LAMP-1–positive endosomes. Similarly, both the kinase activity and the sorting signal present in PI4KIIα are necessary to rescue endosomal PI4KIIα siRNA-induced mutant phenotypes. We propose a mechanism whereby adaptors use canonical sorting motifs to selectively recruit a regulatory enzymatic activity to restricted membrane domains.

Regulation and recruitment of phosphatidylinositol 4-kinase on immature secretory granules is independent of ADP-ribosylation factor 1

2002 ◽  
Vol 363 (2) ◽  
pp. 289-295 ◽  
Author(s):  
Christina PANARETOU ◽  
Sharon A. TOOZE
Keyword(s):  
Kinase Activity ◽  
Secretory Granules ◽  
Specific Inhibitor ◽  
Small Gtpases ◽  
Type Ii ◽  
Adp Ribosylation ◽  
Lipid Kinases ◽  
Phosphatidylinositol 4 ◽  
Golgi Network ◽  
Adp Ribosylation Factor

Heterotrimeric G-proteins, as well as small GTPases of the Rho and ADP-ribosylation factor (ARF) family, are implicated in the regulation of lipid kinases, including PtdIns 4-kinases and PtdIns(4)P 5-kinases. Here, we describe a PtdIns 4-kinase activity on immature secretory granules (ISGs), regulated secretory organelles formed from the trans-Golgi network (TGN), and investigate the regulation of PtdIns4P levels on these membranes. Over 50% of the PtdIns 4-kinase activity on ISGs is inhibited by both a low concentration of adenosine and the monoclonal antibody 4C5G, a specific inhibitor of the type II PtdIns 4-kinase. Treatment of ISGs with mastoparan 7 (M7) stimulates the type II PtdIns 4-kinase via pertussis-toxin-sensitive Gi/G0 proteins, which, in contrast with previous results obtained with chromaffin granules [Gasman, Chasserot-Golaz, Hubert, Aunis and Bader (1998) J. Biol. Chem. 273, 16913–16920], does not require Rho A, B or C. M7 treatment also leads to an inhibition in the recruitment of ARF to ISG membranes: this inhibition is not dependent on Gi/G0 activation, and is not linked to the stimulation of PtdIns 4-kinase observed with M7. PtdIns 4-kinase activity on ISGs is not regulated by myristoylated ARF1—GTP, in contrast with results obtained with Golgi membranes [Godi, Pertile, Meyers, Marra, Di Tullio, Iurisci, Luini, Corda and De Matteis (1999) Nat. Cell Biol. 1, 280–287; Jones, Morris, Morgan, Kondo, Irvine and Cockcroft (2000) J. Biol. Chem. 275, 13962–13170], whereas ARF1—GTP does regulate the production of PtdIns(4,5)P2. Our results suggest that the regulation of PtdIns 4-kinase on the ISGs differs in comparison with that on the TGN, and might be related to a specific requirement of ISG maturation.

scholarly journals Regulation of human type II phosphatidylinositol kinase activity by epidermal growth factor-dependent phosphorylation and receptor association.

1994 ◽  
Vol 269 (49) ◽  
pp. 31243-31251
Author(s):  
A Kauffmann-Zeh ◽  
R Klinger ◽  
G Endemann ◽  
M D Waterfield ◽  
R Wetzker ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Kinase Activity ◽  
Type Ii ◽  
Human Type ◽  
Phosphatidylinositol Kinase ◽  
Epidermal Growth

scholarly journals Cloning of a Human Type II Phosphatidylinositol 4-Kinase Reveals a Novel Lipid Kinase Family

2001 ◽  
Vol 276 (20) ◽  
pp. 16635-16640 ◽  
Author(s):  
Shane Minogue ◽  
J. Simon Anderson ◽  
Mark G. Waugh ◽  
Maria dos Santos ◽  
Steven Corless ◽  
...  
Keyword(s):  
Type Ii ◽  
Lipid Kinase ◽  
Human Type ◽  
Kinase Family ◽  
Phosphatidylinositol 4

scholarly journals Purification and partial characterization of the phosphatidylinositol 4-phosphate kinase from rat brain

1984 ◽  
Vol 223 (1) ◽  
pp. 197-203 ◽  
Author(s):  
C J Van Dongen ◽  
H Zwiers ◽  
W H Gispen
Keyword(s):  
Rat Brain ◽  
Isoelectric Focusing ◽  
Column Chromatography ◽  
Kinase Activity ◽  
Deae Cellulose ◽  
Synaptic Membranes ◽  
Purification Procedure ◽  
Deae Cellulose Column ◽  
Phosphatidylinositol 4 ◽  
Cellulose Column

Phosphatidylinositol 4-phosphate (PtdIns4P) kinase was purified from cytosolic and particulate material of rat brain. The purification procedure of the enzyme from cytosol consisted of (NH4)2SO4 precipitation. DEAE-cellulose column chromatography and preparative isoelectric focusing. Other methods after DEAE-cellulose column chromatography failed to achieve further purification of the PtdIns4P kinase, probably caused by the tendency of the enzyme to aggregate with contaminating proteins. The final purification was 67-fold, and the recovery was 0.6%. After isoelectric focusing the fraction containing the highest PtdIns4P kinase activity showed only one protein as visualized by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and silver staining. The apparent Mr of this protein was 45 kDa and the isoelectric point about 5.8. The activity of PtdIns4P kinase was dependent on the concentration of divalent cations in the incubation medium. PtdIns4P kinase activity was found to be optimal at 10-30 mM-Mg2+. In an attempt to compare the cytosolic with the membrane-derived kinase activity, a Triton/KCl extract from synaptic membranes was subjected to the same purification procedure as the cytosolic enzyme. A difference in isoelectric focusing was observed, possibly due to a higher tendency to form aggregates. However, we tend to conclude that also in the membranes the PtdIns4P kinase activity is present as a 45 kDa protein, identical with that found in the cytosol.

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