Phosphatidylinositol-4-kinase type III beta

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.

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A monoclonal antibody distinguishes two types of phosphatidylinositol 4-kinase

Biochemical Journal ◽

10.1042/bj2730063 ◽

1991 ◽

Vol 273 (1) ◽

pp. 63-66 ◽

Cited By ~ 35

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.

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Arabidopsis Type-III Phosphatidylinositol 4-Kinases β1 and β2 are Upstream of the Phospholipase C Pathway Triggered by Cold Exposure

Plant and Cell Physiology ◽

10.1093/pcp/pcs011 ◽

2012 ◽

Vol 53 (3) ◽

pp. 565-576 ◽

Cited By ~ 46

Author(s):

Elise Delage ◽

Eric Ruelland ◽

Isabelle Guillas ◽

Alain Zachowski ◽

Juliette Puyaubert

Keyword(s):

Phospholipase C ◽

Cold Exposure ◽

Type Iii ◽

Phosphatidylinositol 4

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Characterization of a Soluble Adrenal Phosphatidylinositol 4-Kinase Reveals Wortmannin Sensitivity of Type III Phosphatidylinositol Kinases†

Biochemistry ◽

10.1021/bi9517493 ◽

1996 ◽

Vol 35 (11) ◽

pp. 3587-3594 ◽

Cited By ~ 79

Author(s):

Gregory J. Downing ◽

Stanley Kim ◽

Satoshi Nakanishi ◽

Kevin J. Catt ◽

Tamas Balla

Keyword(s):

Type Iii ◽

Phosphatidylinositol Kinases ◽

Phosphatidylinositol 4

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Differential Regulation of Two Arabidopsis Type III Phosphatidylinositol 4-Kinase Isoforms. A Regulatory Role for the Pleckstrin Homology Domain

PLANT PHYSIOLOGY ◽

10.1104/pp.103.021758 ◽

2003 ◽

Vol 132 (2) ◽

pp. 1053-1064 ◽

Cited By ~ 29

Author(s):

Jill Stevenson-Paulik ◽

John Love ◽

Wendy F. Boss

Keyword(s):

Differential Regulation ◽

Regulatory Role ◽

Pleckstrin Homology Domain ◽

Pleckstrin Homology ◽

Type Iii ◽

Phosphatidylinositol 4

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Regulation of the Plasma Membrane Type III Phosphatidylinositol 4-Kinase by Positively Charged Compounds

Archives of Biochemistry and Biophysics ◽

10.1006/abbi.1994.1366 ◽

1994 ◽

Vol 313 (1) ◽

pp. 112-119 ◽

Cited By ~ 7

Author(s):

W.N. Yang ◽

W.F. Boss

Keyword(s):

Plasma Membrane ◽

Type Iii ◽

Membrane Type ◽

Phosphatidylinositol 4 ◽

Positively Charged

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A Plasma Membrane Pool of Phosphatidylinositol 4-Phosphate Is Generated by Phosphatidylinositol 4-Kinase Type-III Alpha: Studies with the PH Domains of the Oxysterol Binding Protein and FAPP1

Molecular Biology of the Cell ◽

10.1091/mbc.e04-07-0578 ◽

2005 ◽

Vol 16 (3) ◽

pp. 1282-1295 ◽

Cited By ~ 188

Author(s):

Andras Balla ◽

Galina Tuymetova ◽

Arnold Tsiomenko ◽

Péter Várnai ◽

Tamas Balla

Keyword(s):

Plasma Membrane ◽

Down Regulation ◽

Type Iii ◽

Oxysterol Binding Protein ◽

Golgi Localization ◽

Cytoplasmic Vesicles ◽

Ph Domains ◽

Phosphatidylinositol 4 ◽

Cellular Compartments ◽

P Distribution

The PH domains of OSBP and FAPP1 fused to GFP were used to monitor PI(4)P distribution in COS-7 cells during manipulations of PI 4-kinase (PI4K) activities. Both domains were associated with the Golgi and small cytoplasmic vesicles, and a small fraction of OSBP-PH was found at the plasma membrane (PM). Inhibition of type-III PI4Ks with 10 μM wortmannin (Wm) significantly reduced but did not abolish Golgi localization of either PH domains. Downregulation of PI4KIIα or PI4KIIIβ by siRNA reduced the localization of the PH domains to the Golgi and in the former case any remaining Golgi localization was eliminated by Wm treatment. PLC activation by Ca2+ ionophores dissociated the domains from all membranes, but after Ca2+ chelation, they rapidly reassociated with the Golgi, the intracellular vesicles and with the PM. PM association of the domains was significantly higher after the Ca2+ transient and was abolished by Wm pretreatment. PM relocalization was not affected by down-regulation of PI4KIIIβ or -IIα, but was inhibited by down-regulation of PI4KIIIα, or by 10 μM PAO, which also inhibits PI4KIIIα. Our data suggest that these PH domains detect PI(4)P formation in extra-Golgi compartments under dynamic conditions and that various PI4Ks regulate PI(4)P synthesis in distinct cellular compartments.

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Potent, selective small molecule inhibitors of type III phosphatidylinositol-4-kinase α- but not β-inhibit the phosphatidylinositol signaling cascade and cancer cell proliferation

Chemical Communications ◽

10.1039/c3cc48391f ◽

2014 ◽

Vol 50 (40) ◽

pp. 5388-5390 ◽

Cited By ~ 17

Author(s):

Michael J. Waring ◽

David M. Andrews ◽

Paul F. Faulder ◽

Vikki Flemington ◽

Jennifer C. McKelvie ◽

...

Keyword(s):

Cell Proliferation ◽

Cancer Cell ◽

Small Molecule ◽

Small Molecule Inhibitors ◽

Signaling Cascade ◽

Cancer Cell Proliferation ◽

Type Iii ◽

Phosphatidylinositol 4

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Maintenance of Hormone-sensitive Phosphoinositide Pools in the Plasma Membrane Requires Phosphatidylinositol 4-Kinase IIIα

Molecular Biology of the Cell ◽

10.1091/mbc.e07-07-0713 ◽

2008 ◽

Vol 19 (2) ◽

pp. 711-721 ◽

Cited By ~ 128

Author(s):

Andras Balla ◽

Yeun Ju Kim ◽

Peter Varnai ◽

Zsofia Szentpetery ◽

Zachary Knight ◽

...

Keyword(s):

Plasma Membrane ◽

Small Interfering Rna ◽

Type Ii ◽

Measurable Effect ◽

Down Regulation ◽

Type Iii ◽

Hormone Sensitive ◽

Phosphatidylinositol 4 ◽

Interfering Rna

Type III phosphatidylinositol (PtdIns) 4-kinases (PI4Ks) have been previously shown to support plasma membrane phosphoinositide synthesis during phospholipase C activation and Ca2+ signaling. Here, we use biochemical and imaging tools to monitor phosphoinositide changes in the plasma membrane in combination with pharmacological and genetic approaches to determine which of the type III PI4Ks (α or β) is responsible for supplying phosphoinositides during agonist-induced Ca2+ signaling. Using inhibitors that discriminate between the α- and β-isoforms of type III PI4Ks, PI4KIIIα was found indispensable for the production of phosphatidylinositol 4-phosphate (PtdIns4P), phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], and Ca2+ signaling in angiotensin II (AngII)-stimulated cells. Down-regulation of either the type II or type III PI4K enzymes by small interfering RNA (siRNA) had small but significant effects on basal PtdIns4P and PtdIns(4,5)P2 levels in 32P-labeled cells, but only PI4KIIIα down-regulation caused a slight impairment of PtdIns4P and PtdIns(4,5)P2 resynthesis in AngII-stimulated cells. None of the PI4K siRNA treatments had a measurable effect on AngII-induced Ca2+ signaling. These results indicate that a small fraction of the cellular PI4K activity is sufficient to maintain plasma membrane phosphoinositide pools, and they demonstrate the value of the pharmacological approach in revealing the pivotal role of PI4KIIIα enzyme in maintaining plasma membrane phosphoinositides.

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