High impact information on ARG82

• The inositol 1,4,5-trisphosphate kinase of this pathway in Saccharomyces cerevisiae, designated Ipk2, was found to be identical to Arg82, a regulator of the transcriptional complex ArgR-Mcm1 [1].
• Inositol polyphosphate multikinase was identified as an enzyme that generates a series of water-soluble inositol phosphates [2].
• We now report the robust, physiologic, and evolutionarily conserved phosphoinositide 3-kinase activity of inositol polyphosphate multikinase, which is localized to nuclei and unaffected by wortmannin [2].
• By contrast, the recruitment of Arg81p and Arg82p was stimulated by exogenous arginine [3].
• The overall structure of Ipk2 is related to inositol trisphosphate 3-kinase [4].

Biological context of ARG82

• In budding yeast, IP(6) synthesis occurs through the sequential phosphorylation of I(1,4,5)P(3) by two gene products, Ipk2 and Ipk1, a IP(3)/IP(4) dual-specificity 6-/3-kinase and an inositol 1,3,4,5,6-pentakisphosphate 2-kinase, respectively [5].
• To reduce IPK2 activity in Rat-1 cells, we introduced vector-based short interference RNA against rIPK2 [6].
• PtdIns(4,5)P2 hydrolysis occurs normally in mutants lacking Arg82p or Ipk1p, but they accumulate no InsP6, showing that these enzymes normally convert the liberated Ins(1,4,5)P3 rapidly and quantitatively to InsP6 [7].
• Arg82p is a bifunctional protein whose inositol polyphosphate kinase activity is essential for nitrogen and PHO gene expression but not for Mcm1p chaperoning in yeast [8].
• In arg82 mutant strains, remodeling of PHO5 promoter chromatin is impaired, and the adenosine triphosphate-dependent chromatin-remodeling complexes SWI/SNF and INO80 are not efficiently recruited to phosphate-responsive promoters [9].

Anatomical context of ARG82

• This pathway was present in wild-type and ipk2 null cells, albeit at low levels as compared with inositol hexakisphosphate synthesis [10].

Associations of ARG82 with chemical compounds

• Collectively our results provide a molecular basis for the synthesis of higher inositol polyphosphates in plants through multiple routes and indicate that the 6-/3-/5-kinase activities found in plant extracts may be encoded by the IPK2 gene class [5].
• Expression of either I(1,4,5)P3 6- or 3-kinase activity rescued growth of ipk2-deficient yeast at high temperatures, whereas only 6-kinase activity enabled growth on ornithine as the sole nitrogen source [10].
• Plc1p, Arg82p, and Kcs1p, enzymes involved in inositol pyrophosphate synthesis, are essential for phosphate regulation and polyphosphate accumulation in Saccharomyces cerevisiae [11].
• Inositol triphosphate (IP(3)) in yeast is rapidly transformed into IP(4) and IP(5) by a dual kinase, Arg82 [12].
• In a genetic selection for budding yeast mutants that were defective in induction of the phosphate-responsive PHO5 gene, we identified mutations in ARG82/IPK2, which encodes a nuclear inositol polyphosphate kinase [9].

Other interactions of ARG82

• We show here that Mcm1p and Arg80p chaperoning by Arg82p does not involve the inositol polyphosphate kinase activity of Arg82p, but requires its polyaspartate domain [8].
• Heterologous expression of dmIpk2, but not dmIP3K, in ipk2 mutant yeast recapitulates phospholipase C-dependent cellular synthesis of IP6 [13].

Analytical, diagnostic and therapeutic context of ARG82

• To define physiologically relevant targets of the catalytic products of Arg82p and Kcs1p, we used DNA microarray technology [8].

References