Abstract

? During the proposed renewal period, we will extend advances made in the preceding five years. These involve a number of areas. Proposals described in detail in the Research Design section include elucidating further our discovery that IP7 physiologically phosphorylates a variety of proteins in diverse species. We will also continue our studies establishing IP6 kinase-2 as a physiologic mediator of cell death. We will clarify our observations that the enzyme we first discovered as inositol polyphosphate multikinase (IPMK) also is a major nuclear PI3-kinase. Additionally, we will move forward working out a novel cell death cascade whereby apoptotic stimuli activate inducible NO synthase to generate NO that S-nitrosylates glyceraldehyde- 3-phosphate dehydrogenase (GAPDH) enabling it to bind Siah, translocate to the nucleus and cause cell death by enhancing the turnover of as yet unspecified proteins. ? ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Award (K05)
Project #
2K05DA000074-26
Application #
6979187
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Pollock, Jonathan D
Project Start
1980-07-01
Project End
2010-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
26
Fiscal Year
2005
Total Cost
$129,276
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Yuan, Guoxiang; Vasavda, Chirag; Peng, Ying-Jie et al. (2015) Protein kinase G-regulated production of H2S governs oxygen sensing. Sci Signal 8:ra37
Peng, Ying-Jie; Makarenko, Vladislav V; Nanduri, Jayasri et al. (2014) Inherent variations in CO-H2S-mediated carotid body O2 sensing mediate hypertension and pulmonary edema. Proc Natl Acad Sci U S A 111:1174-9
Bang, Sookhee; Kim, Seyun; Dailey, Megan J et al. (2012) AMP-activated protein kinase is physiologically regulated by inositol polyphosphate multikinase. Proc Natl Acad Sci U S A 109:616-20
Dailey, Megan J; Kim, Seyun (2012) Inositol polyphosphate multikinase: an emerging player for the central action of AMP-activated protein kinase. Biochem Biophys Res Commun 421:1-3
Kim, Seyun; Kim, Sangwon F; Maag, David et al. (2011) Amino acid signaling to mTOR mediated by inositol polyphosphate multikinase. Cell Metab 13:215-21
Maag, David; Maxwell, Micah J; Hardesty, Douglas A et al. (2011) Inositol polyphosphate multikinase is a physiologic PI3-kinase that activates Akt/PKB. Proc Natl Acad Sci U S A 108:1391-6
Ho, Gary P H; Selvakumar, Balakrishnan; Mukai, Jun et al. (2011) S-nitrosylation and S-palmitoylation reciprocally regulate synaptic targeting of PSD-95. Neuron 71:131-41
Mustafa, Asif K; Sikka, Gautam; Gazi, Sadia K et al. (2011) Hydrogen sulfide as endothelium-derived hyperpolarizing factor sulfhydrates potassium channels. Circ Res 109:1259-68
Sen, Nilkantha; Snyder, Solomon H (2010) Protein modifications involved in neurotransmitter and gasotransmitter signaling. Trends Neurosci 33:493-502
Paul, B D; Snyder, S H (2010) The unusual amino acid L-ergothioneine is a physiologic cytoprotectant. Cell Death Differ 17:1134-40

Showing the most recent 10 out of 28 publications