Nuclear targeting of the β isoform of Type II phosphatidylinositol phosphate kinase (phosphatidylinositol 5-phosphate 4-kinase) by its α-helix 7

CIRUELA, Antonio; Hinchliffe, Katherine A.; Divecha, Nullin; Irvine, Robin F.

doi:10.1042/0264-6021:3460587

Cited by 59 publications

(68 citation statements)

References 6 publications

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“…1A). These results are consistent with previous reports that an acidic ␣-helix within the kinase insert domain promotes nuclear targeting of PIPKII␤ (36,37). To determine whether the PIPKII␤ kinase insert domain is sufficient for PIPKII␤ nuclear targeting, the kinase insert was fused to LacZ, and its subcellular localization was examined.…”

Section: The Kinase Insert Domain Of Pipkii␤ Is Necessary and Sufficisupporting

confidence: 83%

Coordinated Activation of the Nuclear Ubiquitin Ligase Cul3-SPOP by the Generation of Phosphatidylinositol 5-Phosphate

Bunce

Boronenkov

Anderson

2008

Journal of Biological Chemistry

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Phosphoinositide signaling pathways regulate numerous processes in eukaryotic cells, including migration, proliferation, and survival. The regulatory lipid phosphatidylinositol 4,5-bisphosphate is synthesized by two distinct classes of phosphatidylinositol phosphate kinases (PIPKs), the type I and II PIPKs. Although numerous physiological functions have been identified for type I PIPKs, little is known about the functions and regulation of type II PIPK. Using a yeast two-hybrid screen, we identified an interaction between the type II␤ PIPK isoform (PIPKII␤) and SPOP (speckle-type POZ domain protein), a nuclear speckle-associated protein that recruits substrates to Cul3-based ubiquitin ligases. PIPKII␤ and SPOP interact and co-localize at nuclear speckles in mammalian cells, and SPOP mediates the ubiquitylation of PIPKII␤ by Cul3-based ubiquitin ligases. Additionally, stimulation of the p38 MAPK pathway enhances the ubiquitin ligase activity of Cul3-SPOP toward multiple substrate proteins. Finally, a kinase-dead PIPKII␤ mutant enhanced ubiquitylation of Cul3-SPOP substrates. The kinase-dead PIPKII␤ mutant increases the cellular content of its substrate lipid phosphatidylinositol 5-phosphate (PI5P), suggesting that PI5P may stimulate Cul3-SPOP activity through a p38-dependent signaling pathway. Expression of phosphatidylinositol-4,5-bisphosphate 4-phosphatases that generate PI5P dramatically stimulated Cul3-SPOP activity and was blocked by the p38 inhibitor SB203580. Taken together, these data define a novel mechanism whereby the phosphoinositide PI5P leads to stimulation of Cul3-SPOP ubiquitin ligase activity and also implicate PIPKII␤ as a key regulator of this signaling pathway through its association with the Cul3-SPOP complex.Phosphoinositide signaling pathways modulate a diverse array of cellular processes in eukaryotes. Modification of the inositol ring by lipid kinases and phosphatases produces distinct phosphatidylinositol phosphate (PIP) 2 isomers. These phosphatidylinositol phosphate isomers in turn selectively modulate the activities of effector proteins. In the cytosol, phosphoinositides regulate numerous processes, including actin polymerization, focal adhesion dynamics, ion channel activity, growth factor receptor signaling, and vesicle trafficking (1-4).In the nucleus, an autonomous phosphoinositide cycle regulates processes, including differentiation, proliferation, cell cycle progression, and apoptosis (5). Phosphatidylinositol 4,5-bisphosphate (PI-4,5-P 2 ) is a critical phosphoinositide in eukaryotic cells. PI-4,5-P 2 is not only itself a potent signaling molecule but is also a precursor of other second messengers such as phosphatidylinositol 3,4,5-trisphosphate, inositol 1,4,5-trisphosphate, and diacylglycerol. Because of its multipotent signaling capacity, the regulated synthesis of PI-4,5-P 2 is essential for eukaryotes. In mammalian cells, PI-4,5-P 2 is synthesized by two classes of phosphatidylinositol phosphate kinases (PIPKs) (6). Type I PIPKs (PIPKIs) preferentially use phosphatidylinos...

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Section: The Kinase Insert Domain Of Pipkii␤ Is Necessary and Sufficisupporting

confidence: 83%

Coordinated Activation of the Nuclear Ubiquitin Ligase Cul3-SPOP by the Generation of Phosphatidylinositol 5-Phosphate

Bunce

Boronenkov

Anderson

2008

Journal of Biological Chemistry

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“…Currently little is known about the roles of these enzymes in cells or if they impact membrane traffic in any way. PIP4K␤ partially localizes to the nucleus (49). A third member of this family, PIP4K␥, has been identified as resident in the ER (159).…”

Section: Pip 4-kinasesmentioning

confidence: 99%

Phosphoinositides in Constitutive Membrane Traffic

Roth

2004

Physiological Reviews

263

267

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Proteins that make, consume, and bind to phosphoinositides are important for constitutive membrane traffic. Different phosphoinositides are concentrated in different parts of the central vacuolar pathway, with phosphatidylinositol 4-phosphate predominate on Golgi, phosphatidylinositol 4,5-bisphosphate predominate at the plasma membrane, phosphatidylinositol 3-phosphate the major phosphoinositide on early endosomes, and phosphatidylinositol 3,5-bisphosphate found on late endocytic organelles. This spatial segregation may be the mechanism by which the direction of membrane traffic is controlled. Phosphoinositides increase the affinity of membranes for peripheral membrane proteins that function for sorting protein cargo or for the docking and fusion of transport vesicles. This implies that constitutive membrane traffic may be regulated by the mechanisms that control the activity of the enzymes that produce and consume phosphoinositides. Although the lipid kinases and phosphatases that function in constitutive membrane traffic are beginning to be identified, their regulation is poorly understood.

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“…A recent report indicates that the N terminus of Arabidopsis PI4P 5-kinase isoform 1 (PIP5K1) has multiple regulatory effects on enzyme activity and may guide subcellular localization of the enzyme . PI4P 5-kinases from different organisms have been reported to associate with different subcellular locations, including the plasma membrane of plants, yeast, and mammals Heilmann et al, 2001;Kobayashi et al, 2005;Santarius et al, 2006), the nucleus of yeast and mammals (Ciruela et al, 2000;Audhya and Emr, 2003;Santarius et al, 2006), the actin cytoskeleton of plants, yeast, and mammals (Desrivieres et al, 1998;Doughman et al, 2003;Davis et al, 2007), and endomembranes of plants and mammals (Whatmore et al, 1996;Heilmann et al, 1999;Im et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

The Type B Phosphatidylinositol-4-Phosphate 5-Kinase 3 Is Essential for Root Hair Formation inArabidopsis thaliana

et al. 2008

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Root hairs are extensions of root epidermal cells and a model system for directional tip growth of plant cells. A previously uncharacterized Arabidopsis thaliana phosphatidylinositol-4-phosphate 5-kinase gene (PIP5K3) was identified and found to be expressed in the root cortex, epidermal cells, and root hairs. Recombinant PIP5K3 protein was catalytically active and converted phosphatidylinositol-4-phosphate to phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P 2 ]. Arabidopsis mutant plants homozygous for T-DNA-disrupted PIP5K3 alleles were compromised in root hair formation, a phenotype complemented by expression of wild-type PIP5K3 cDNA under the control of a 1500-bp PIP5K3 promoter fragment. Root hair-specific PIP5K3 overexpression resulted in root hair deformation and loss of cell polarity with increasing accumulation of PIP5K3 transcript. Using reestablishment of root hair formation in T-DNA mutants as a bioassay for physiological functionality of engineered PIP5K3 variants, catalytic activity was found to be essential for physiological function, indicating that PtdIns(4,5)P 2 formation is required for root hair development. An N-terminal domain containing membrane occupation and recognition nexus repeats, which is not required for catalytic activity, was found to be essential for the establishment of root hair growth. Fluorescencetagged PIP5K3 localized to the periphery of the apical region of root hair cells, possibly associating with the plasma membrane and/or exocytotic vesicles. Transient heterologous expression of full-length PIP5K3 in tobacco (Nicotiana tabacum) pollen tubes increased plasma membrane association of a PtdIns(4,5)P 2 -specific reporter in these tip-growing cells. The data demonstrate that root hair development requires PIP5K3-dependent PtdIns(4,5)P 2 production in the apical region of root hair cells.

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Nuclear targeting of the β isoform of Type II phosphatidylinositol phosphate kinase (phosphatidylinositol 5-phosphate 4-kinase) by its α-helix 7

Cited by 59 publications

References 6 publications

Coordinated Activation of the Nuclear Ubiquitin Ligase Cul3-SPOP by the Generation of Phosphatidylinositol 5-Phosphate

Coordinated Activation of the Nuclear Ubiquitin Ligase Cul3-SPOP by the Generation of Phosphatidylinositol 5-Phosphate

Phosphoinositides in Constitutive Membrane Traffic

The Type B Phosphatidylinositol-4-Phosphate 5-Kinase 3 Is Essential for Root Hair Formation inArabidopsis thaliana

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