Abstract

The goal of the proposed experiments is to elucidate the structure and function of phosphatidylinositol-phosphate kinases (PIPKs) in the nucleus. During the previous grant period, Dr. Anderson defined type I and II PIP5Ks, novel lipid kinases, which also produce PI3, 4P2 and PI3, 4,5, P2. Localization experiments demonstrated that PIPKs and PIP2 are co-localized in a distinctive pattern termed """"""""nuclear speckle"""""""" within the nucleus and that these compounds participate in novel nuclear phosphoinositide signaling pathways. To test this hypothesis, the proposal has three specific aims.
Aim 1 will identify the nuclear localization sequences within PIP5KII and determine whether nuclear localization of this kinase is regulated.
In Aim 2, mutants of PIPKs will be generated, and their effect on nuclear signaling pathways will be determined. Additional experiments will focus on identifying and characterizing nuclear proteins that interact with PIPKs. Experiments proposed in Aim 3 will further characterize the nuclear compartment containing the PIPKs by biochemical and photochemical methods.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM051968-06
Application #
6180597
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Ikeda, Richard A
Project Start
1994-12-01
Project End
2002-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
6
Fiscal Year
2000
Total Cost
$242,492
Indirect Cost

  Institution

Name
University of Wisconsin Madison
Department
Pharmacology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715

  Publications

Li, Weimin; Li, Wencheng; Laishram, Rakesh S et al. (2017) Distinct regulation of alternative polyadenylation and gene expression by nuclear poly(A) polymerases. Nucleic Acids Res 45:8930-8942
Thapa, Narendra; Tan, Xiaojun; Choi, Suyong et al. (2016) The Hidden Conundrum of Phosphoinositide Signaling in Cancer. Trends Cancer 2:378-390
Choi, Suyong; Anderson, Richard A (2016) IQGAP1 is a phosphoinositide effector and kinase scaffold. Adv Biol Regul 60:29-35
Choi, Suyong; Hedman, Andrew C; Sayedyahossein, Samar et al. (2016) Agonist-stimulated phosphatidylinositol-3,4,5-trisphosphate generation by scaffolded phosphoinositide kinases. Nat Cell Biol 18:1324-1335
Tan, Xiaojun; Lambert, Paul F; Rapraeger, Alan C et al. (2016) Stress-Induced EGFR Trafficking: Mechanisms, Functions, and Therapeutic Implications. Trends Cell Biol 26:352-366
Choi, Suyong; Thapa, Narendra; Tan, Xiaojun et al. (2015) PIP kinases define PI4,5P?signaling specificity by association with effectors. Biochim Biophys Acta 1851:711-23
Mohan, Nimmy; Sudheesh, A P; Francis, Nimmy et al. (2015) Phosphorylation regulates the Star-PAP-PIPKI? interaction and directs specificity toward mRNA targets. Nucleic Acids Res 43:7005-20
Li, W; Anderson, R A (2014) Star-PAP controls HPV E6 regulation of p53 and sensitizes cells to VP-16. Oncogene 33:928-32
Li, Weimin; Laishram, Rakesh S; Anderson, Richard A (2013) The novel poly(A) polymerase Star-PAP is a signal-regulated switch at the 3'-end of mRNAs. Adv Biol Regul 53:64-76
Ray, Debashish; Kazan, Hilal; Cook, Kate B et al. (2013) A compendium of RNA-binding motifs for decoding gene regulation. Nature 499:172-7

Showing the most recent 10 out of 31 publications