The β-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 PIP4Kβ 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 PIP4Kβ interacts in vitro and in vivo with the PIP4Kα 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 PIP4Kβ has 2000-fold less activity towards PtdIns5P compared with PIP4Kα, and that the majority of PIP4K activity associated with PIP4Kβ comes from its interaction with PIP4Kα. Furthermore, PIP4Kβ can modulate the nuclear localization of PIP4Kα, and PIP4Kα has a role in regulating PIP4Kβ functions. The results of the present study suggest a rationale for the functional interaction between PIP4Kα and PIP4Kβ and provide insight into how the relative levels of the two enzymes may be important in their physiological and pathological roles.
Skip Nav Destination
Article navigation
September 2010
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
August 13 2010
PIP4Kβ interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kα
Yvette Bultsma;
Yvette Bultsma
1
1CRUK Inositide Laboratory, the Paterson Institute for Cancer Research, Wilmslow Road, Manchester M20 4BX, U.K.
Search for other works by this author on:
Willem-Jan Keune;
Willem-Jan Keune
1
1CRUK Inositide Laboratory, the Paterson Institute for Cancer Research, Wilmslow Road, Manchester M20 4BX, U.K.
Search for other works by this author on:
Nullin Divecha
2To whom correspondence should be addressed (email ndivecha@picr.man.ac.uk).
Search for other works by this author on:
Biochem J (2010) 430 (2): 223–235.
Article history
Received:
March 08 2010
Revision Received:
June 07 2010
Accepted:
June 28 2010
Accepted Manuscript online:
June 28 2010
Citation
Yvette Bultsma, Willem-Jan Keune, Nullin Divecha; PIP4Kβ interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kα. Biochem J 1 September 2010; 430 (2): 223–235. doi: https://doi.org/10.1042/BJ20100341
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.