Nuclear targeting of the beta isoform of type II phosphatidylinositol phosphate kinase (phosphatidylinositol 5-phosphate 4-kinase) by its alpha-helix 7
Nuclear targeting of the beta isoform of type II phosphatidylinositol phosphate kinase (phosphatidylinositol 5-phosphate 4-kinase) by its alpha-helix 7
Type II phosphatidylinositol phosphate kinases (PIPkins) have recently been found to be primarily phosphatidylinositol 5-phosphate 4-kinases, and their physiological role remains unclear. We have previously shown that a Type II PIPkin [isoform(s) unknown], is localized partly in the nucleus [Divecha, Rhee, Letcher and Irvine (1993) Biochem. J. 289, 617-620], and here we show, by transfection of HeLa cells with green-fluorescent-protein-tagged Type II PIPkins, that this is likely to be the Type IIbeta isoform. Type IIbeta PIPkin has no obvious nuclear localization sequence, and a detailed analysis of the localization of chimaeras and mutants of the alpha (cytosolic) and beta PIPkins shows that the nuclear localization requires the presence of a 17-amino-acid length of alpha-helix (alpha-helix 7) that is specific to the beta isoform, and that this helix must be present in its entirety, with a precise orientation. This resembles the nuclear targeting of the HIV protein Vpr, and Type IIbeta PIPkin is apparently therefore the first example of a eukaryotic protein that uses the same mechanism.
Amino Acid Sequence Cell Nucleus/*enzymology Green Fluorescent Proteins HeLa Cells Humans Isoenzymes/*metabolism Luminescent Proteins/metabolism Minor Histocompatibility Antigens Molecular Sequence Data Phosphotransferases (Alcohol Group Acceptor)/chemistry/*metabolism Protein Structure, Secondary Sequence Homology, Amino Acid
587-591
Ciruela, A.
41840163-24ea-4f38-9e5f-718245a0555a
Hinchliffe, K. A.
2a02065f-04cf-49bc-9ff6-da0030f3ed2f
Divecha, N.
5c2ad0f8-4ce7-405f-8a15-2fc4ab96d787
Irvine, R. F.
a8a94b1b-419c-4262-b745-eae1941ce145
15 March 2000
Ciruela, A.
41840163-24ea-4f38-9e5f-718245a0555a
Hinchliffe, K. A.
2a02065f-04cf-49bc-9ff6-da0030f3ed2f
Divecha, N.
5c2ad0f8-4ce7-405f-8a15-2fc4ab96d787
Irvine, R. F.
a8a94b1b-419c-4262-b745-eae1941ce145
Ciruela, A., Hinchliffe, K. A., Divecha, N. and Irvine, R. F.
(2000)
Nuclear targeting of the beta isoform of type II phosphatidylinositol phosphate kinase (phosphatidylinositol 5-phosphate 4-kinase) by its alpha-helix 7.
Biochemical Journal, 346 (Pt 3), .
Abstract
Type II phosphatidylinositol phosphate kinases (PIPkins) have recently been found to be primarily phosphatidylinositol 5-phosphate 4-kinases, and their physiological role remains unclear. We have previously shown that a Type II PIPkin [isoform(s) unknown], is localized partly in the nucleus [Divecha, Rhee, Letcher and Irvine (1993) Biochem. J. 289, 617-620], and here we show, by transfection of HeLa cells with green-fluorescent-protein-tagged Type II PIPkins, that this is likely to be the Type IIbeta isoform. Type IIbeta PIPkin has no obvious nuclear localization sequence, and a detailed analysis of the localization of chimaeras and mutants of the alpha (cytosolic) and beta PIPkins shows that the nuclear localization requires the presence of a 17-amino-acid length of alpha-helix (alpha-helix 7) that is specific to the beta isoform, and that this helix must be present in its entirety, with a precise orientation. This resembles the nuclear targeting of the HIV protein Vpr, and Type IIbeta PIPkin is apparently therefore the first example of a eukaryotic protein that uses the same mechanism.
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Published date: 15 March 2000
Additional Information:
Ciruela, A Hinchliffe, K A Divecha, N Irvine, R F eng Research Support, Non-U.S. Gov't England 2000/03/04 Biochem J. 2000 Mar 15;346 Pt 3(Pt 3):587-91.
Keywords:
Amino Acid Sequence Cell Nucleus/*enzymology Green Fluorescent Proteins HeLa Cells Humans Isoenzymes/*metabolism Luminescent Proteins/metabolism Minor Histocompatibility Antigens Molecular Sequence Data Phosphotransferases (Alcohol Group Acceptor)/chemistry/*metabolism Protein Structure, Secondary Sequence Homology, Amino Acid
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Local EPrints ID: 480100
URI: http://eprints.soton.ac.uk/id/eprint/480100
ISSN: 0264-6021
PURE UUID: e9dcaf9b-b12f-43f5-b6fe-b90e291feadf
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Date deposited: 01 Aug 2023 16:48
Last modified: 17 Mar 2024 02:59
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Author:
A. Ciruela
Author:
K. A. Hinchliffe
Author:
R. F. Irvine
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