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A Conserved Family of Enzymes That Phosphorylate Inositol Hexakisphosphate
Sashidhar Mulugu,1*Wenli Bai,1Peter C. Fridy,1Robert J. Bastidas,1James C. Otto,1D. Eric Dollins,1Timothy A. Haystead,2Anthony A. Ribeiro,3John D. York1
Inositol pyrophosphates are a diverse group of high-energy signalingmolecules whose cellular roles remain an active area of study.We report a previously uncharacterized class of inositol pyrophosphatesynthase and find it is identical to yeast Vip1 and Asp1 proteins,regulators of actin-related protein-2/3 (ARP 2/3) complexes.Vip1 and Asp1 acted as enzymes that encode inositol hexakisphosphate(IP6) and inositol heptakisphosphate (IP7) kinase activities.Alterations in kinase activity led to defects in cell growth,morphology, and interactions with ARP complex members. The functionalityof Asp1 and Vip1 may provide cells with increased signalingcapacity through metabolism of IP6.
1 Howard Hughes Medical Institute, Department of Pharmacology and Cancer Biology, Duke University Medical Center, DUMC 3813, Durham, NC 27710, USA. 2 Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. 3 Department of Biochemistry, NMR Center, Duke University Medical Center, Durham, NC 27710, USA.
* Present address: Bharathidasan University, Tiruchirappalli,620 024, India.
To whom correspondence should be addressed. E-mail: yorkj{at}duke.edu
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