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PIP4Kbeta interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kalpha

PIP4Kbeta interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kalpha
PIP4Kbeta interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kalpha
The beta-isoform of PIP4K (PtdIns5P-4-kinase) regulates the levels of nuclear PtdIns5P, which in turn modulates the acetylation of the tumour suppressor p53. The crystal structure of PIP4Kbeta demonstrated that it can form a homodimer with the two subunits arranged in opposite orientations. Using MS, isoform-specific antibodies against PIP4Ks, RNAi (RNA interference) suppression and overexpression studies, we show that PIP4Kbeta interacts in vitro and in vivo with the PIP4Kalpha isoform. As the two isoforms phosphorylate the same substrate to generate the same product, the interaction could be considered to be functionally redundant. However, contrary to expectation, we find that PIP4Kbeta has 2000-fold less activity towards PtdIns5P compared with PIP4Kalpha, and that the majority of PIP4K activity associated with PIP4Kbeta comes from its interaction with PIP4Kalpha. Furthermore, PIP4Kbeta can modulate the nuclear localization of PIP4Kalpha, and PIP4Kalpha has a role in regulating PIP4Kbeta functions. The results of the present study suggest a rationale for the functional interaction between PIP4Kalpha and PIP4Kbeta and provide insight into how the relative levels of the two enzymes may be important in their physiological and pathological roles.
phosphoinositide, ptdIns(4, 5)P2, ptdIns5P, ptdIns5P kinase
1470-8728
223-235
Bultsma, Yvette
21f6f52e-dd7f-4018-8741-e756d8697d2a
Keune, Willem-Jan
b72d28ff-c2fa-4a86-bfa6-8452126ba844
Divecha, Nullin
5c2ad0f8-4ce7-405f-8a15-2fc4ab96d787
Bultsma, Yvette
21f6f52e-dd7f-4018-8741-e756d8697d2a
Keune, Willem-Jan
b72d28ff-c2fa-4a86-bfa6-8452126ba844
Divecha, Nullin
5c2ad0f8-4ce7-405f-8a15-2fc4ab96d787

Bultsma, Yvette, Keune, Willem-Jan and Divecha, Nullin (2010) PIP4Kbeta interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kalpha. Biochemical Journal, 430 (2), 223-235. (doi:10.1042/BJ20100341). (PMID:20583997)

Record type: Article

Abstract

The beta-isoform of PIP4K (PtdIns5P-4-kinase) regulates the levels of nuclear PtdIns5P, which in turn modulates the acetylation of the tumour suppressor p53. The crystal structure of PIP4Kbeta demonstrated that it can form a homodimer with the two subunits arranged in opposite orientations. Using MS, isoform-specific antibodies against PIP4Ks, RNAi (RNA interference) suppression and overexpression studies, we show that PIP4Kbeta interacts in vitro and in vivo with the PIP4Kalpha isoform. As the two isoforms phosphorylate the same substrate to generate the same product, the interaction could be considered to be functionally redundant. However, contrary to expectation, we find that PIP4Kbeta has 2000-fold less activity towards PtdIns5P compared with PIP4Kalpha, and that the majority of PIP4K activity associated with PIP4Kbeta comes from its interaction with PIP4Kalpha. Furthermore, PIP4Kbeta can modulate the nuclear localization of PIP4Kalpha, and PIP4Kalpha has a role in regulating PIP4Kbeta functions. The results of the present study suggest a rationale for the functional interaction between PIP4Kalpha and PIP4Kbeta and provide insight into how the relative levels of the two enzymes may be important in their physiological and pathological roles.

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More information

e-pub ahead of print date: 28 June 2010
Published date: 1 September 2010
Keywords: phosphoinositide, ptdIns(4, 5)P2, ptdIns5P, ptdIns5P kinase
Organisations: Molecular and Cellular

Identifiers

Local EPrints ID: 372332
URI: http://eprints.soton.ac.uk/id/eprint/372332
ISSN: 1470-8728
PURE UUID: f1093728-f86b-4c9e-929c-c6d8062c20c6

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Date deposited: 10 Dec 2014 12:51
Last modified: 15 Jul 2019 21:37

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Contributors

Author: Yvette Bultsma
Author: Willem-Jan Keune
Author: Nullin Divecha

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