HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 277, Issue 36, 32730-32738, September 6, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/36/32730    most recent M205476200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hidaka, K. Articles by Shears, S. B. Search for Related Content PubMed PubMed Citation Articles by Hidaka, K. Articles by Shears, S. B. Social Bookmarking                      What's this?

An Adjacent Pair of Human NUDT Genes on Chromosome X Are Preferentially Expressed in Testis and Encode Two New Isoforms of Diphosphoinositol Polyphosphate Phosphohydrolase^*

Kiyoshi Hidaka^§, James J. Caffrey^§¶, Len Hua, Tong Zhang, J. R. Falck, Gabrielle C. Nickel^**, Laura Carrel^**, Larry D. Barnes, and Stephen B. Shears^§§

From the  Inositide Signaling Section, Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, the  Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, the ^** Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4955, and the  Department of Biochemistry, University of Texas Health Science Center, San Antonio, Texas 78229-3900

Combinatorial expression of the various isoforms of diphosphoinositol synthases and phosphohydrolases determines the rates of phosphorylation/dephosphorylation cycles that have been functionally linked to vesicle trafficking, stress responses, DNA repair, and apoptosis. We now describe two new 19-kDa diphosphoinositol polyphosphate phosphohydrolases (DIPPs), named types 3 and 3, which possess the canonical Nudix-type catalytic motif flanked on either side by short Gly-rich sequences. The two enzymes differ only in that Pro-89 in the  form is replaced by Arg-89 in the  form, making the latter ~2-fold more active in vitro. Another Nudix substrate, diadenosine hexaphosphate, was hydrolyzed less efficiently (k_cat/K_m = 0.2 × 10⁵ M¹ s¹) compared with diphosphoinositol polyphosphates (k_cat/K_m = 2-40 × 10⁵ M¹ s¹). Catalytic activity in vivo was established by individual overexpression of the human (h) DIPP3 isoforms in HEK293 cells, which reduced cellular levels of diphosphoinositol polyphosphates by 40-50%. The hDIPP3 mRNA is preferentially expressed in testis, accompanied by relatively weak expression in the brain, contrasting with hDIPP1 and hDIPP2 which are widely expressed. The hDIPP3 genes (NUDT10 encodes hDIPP3; NUDT11 encodes hDIPP3) are only 152 kbp apart at p11.22 on chromosome X and probably arose by duplication. Transcription of both genes is inactivated on one of the X chromosomes of human females to maintain appropriate gene dosage. The hDIPP3 pair add tissue-specific diversity to the molecular mechanisms regulating diphosphoinositol polyphosphate turnover.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				J. H. Choi, J. Williams, J. Cho, J. R. Falck, and S. B. Shears Purification, Sequencing, and Molecular Identification of a Mammalian PP-InsP5 Kinase That Is Activated When Cells Are Exposed to Hyperosmotic Stress J. Biol. Chem., October 19, 2007; 282(42): 30763 - 30775. [Abstract] [Full Text] [PDF]

				D. I. Fisher, S. T. Safrany, P. Strike, A. G. McLennan, and J. L. Cartwright Nudix Hydrolases That Degrade Dinucleoside and Diphosphoinositol Polyphosphates Also Have 5-Phosphoribosyl 1-Pyrophosphate (PRPP) Pyrophosphatase Activity That Generates the Glycolytic Activator Ribose 1,5-Bisphosphate J. Biol. Chem., November 27, 2002; 277(49): 47313 - 47317. [Abstract] [Full Text] [PDF]