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Science 6 April 2007:
Vol. 316. no. 5821, pp. 106 - 109
DOI: 10.1126/science.1139099
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Reports

A Conserved Family of Enzymes That Phosphorylate Inositol Hexakisphosphate

Sashidhar Mulugu,1* Wenli Bai,1 Peter C. Fridy,1 Robert J. Bastidas,1 James C. Otto,1 D. Eric Dollins,1 Timothy A. Haystead,2 Anthony A. Ribeiro,3 John D. York1{dagger}

Inositol pyrophosphates are a diverse group of high-energy signaling molecules whose cellular roles remain an active area of study. We report a previously uncharacterized class of inositol pyrophosphate synthase 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 functionality of Asp1 and Vip1 may provide cells with increased signaling capacity 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.

{dagger} To whom correspondence should be addressed. E-mail: yorkj{at}duke.edu

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