ABSTRACT
Inositol 1,4,5-trisphosphate 3-kinase (IP3 3-kinase/IP3K) plays an important role in signal transduction in animal cells by phosphorylating inositol 1,4,5-trisphosphate (IP3) to inositol 1,3,4,5-tetrakisphosphate (IP4). Both IP3 and IP4 are critical second messengers which regulate calcium (Ca2+) homeostasis. Mammalian IP3Ks are involved in many biological processes, including brain development, memory, learning and so on. It is widely reported that Ca2+ is a canonical second messenger in higher plants. Therefore, plant IP3K should also play a crucial role in plant development. Recently, we reported the identification of plant IP3K gene (AtIpk2β/AtIP3K) from Arabidopsis thaliana and its characterization. Here, we summarize the molecular cloning, biochemical properties and biological functions of IP3Ks from animal, yeast and plant. This review also discusses potential functions of IP3Ks in signaling crosstalk, inositol phosphate metabolism, gene transcriptional control and so on.
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INTRODUCTION
Inositol 1,4,5-trisphosphate (IP3) is an important second messenger in animal cells that mediates calcium (Ca2+) release from the endoplasmic reticulum (ER) to the cytosol 1, 2, 3. Inositol 1,3,4,5-tetrakisphopsphate (IP4) is another messenger responsible for mediating Ca2+ entry through plasma membrane and mobilize intracellular Ca2+ by acting synergistically with IP3 4. Inositol 1,4,5-trisphosphate 3-kinase (IP3 3-kinase/IP3K) phosphorylates IP3 to IP4 1, 5. Thus, IP3K plays a key role in maintaining Ca2+ homeostasis by regulating the concentrations of IP3 and IP4.
IP3 also serves as a precursor for the synthesis of other higher inositol phosphate (IP) isomers in IP metabolism 6, 7. These water-soluble IP isomers are involved in multiple cellular events such as modulating Ras GTPase-activating protein 8, blocking tumor cell growth 9, regulating mRNA export 10 and so on. In addition, inositol 1,2,3,4,5,6-hexakisphosphate (IP6) is related to human neutrophil function 11 and plant seed germination 12, 13. Yeast and Arabidopsis IP3Ks, also referred to as inositol polyphosphate kinase (Ipk) and inositol phosphate multikinase (Ipmk), recognize IP3 as substrate and add a phosphate to position 6 on the inositol ring to generate inositol 1,4,5,6-tetrakisphosphate (I(1,4,5,6)P4) 10, 14, 15. It is further phosphorylated by yeast and Arabidopsis IP3Ks to produce inositol 1,3,4,5,6-pentakisphosphate (IP5) 10, 14, 15. Therefore, the physiological function of IP3K is not only regulating intracellular Ca2+ homeostasis, but also controlling IP metabolism (Fig. 1).
MOLECULAR CLONING OF IP3K
Inostiol 1,4,5-trisphosphate 3-kinase (IP3 3-kinase)
The first IP3 3-kinase cDNA (RnIP33K-A) was isolated from rat brain in 1990 16, 17, 18. Afterwards, several cDNAs encoding IP3 3-kinase were consequently cloned from human (HsIP33K-A, HsIP33K-B, HsIP33K-C) and rat (RnIP33K-B, RnIP33K-C) 19, 20, 21, 22, 23. Rat RnIP33K-B is 204 amino acids longer than that of the human HsIP33K-B, but remaining similar to its human homologue with 93% identity in amino acids 21. The recently identified human HsIP33K-C shares a highly conserved catalytic domain with human isoforms A and B 22, 23. It is about 75% identical to rat RnIP33K-C 22, 23. IP3 3-kinase from chicken 24, nematode 25 and fruit fly 26 has also been identified.
There are at least three distinct IP3 3-kinase isoforms (A, B, and C). They are different in their molecular masses, Ca2+/calmodulin (Ca2+/CaM) sensitivity, intracellular distribution and tissue expression 23, 27 (Tab. 1). Mammalian IP3 3-kinases are usually activated by Ca2+/ CaM 28. Nematode IP3 3-kinase instead lacks a consensus CaM-binding site and thus is insensitive to Ca2+/CaM 25. There are evidences suggesting that the N-terminal sequence of IP3 3-kinases is involved in intracellular localization 27, 29. For example, the N-terminal 320 amino acid sequence of rat RnIP33K-B is unique and is necessary for the binding of rat RnIP33K-B to the cytosolic face of the ER membrane 30. IP3 3-kinase isoforms show tissue specificity, such as rat RnIP33K-A is specifically expressed in brain and testes, whereas rat RnIP33K-B is predominantly expressed in lung and also in thymus, heart, testes and brain 29. Such specified distribution and expression pattern of IP3 3-kinases may contribute to their various physiological functions. However, all these IP3 3-kinases seem to have strict biochemical activity in phosphorylating IP3 to IP4 25, 26, 27.
Inositol phosphate multikinase (Ipmk)/inositol polyphosphate kinase (Ipk)
Inositol phosphate multikinase (Ipmk) is widely distributed in the kingdoms of animal, plant and yeast 31. The first identified Ipmk cDNA (also called Ipk2) was from yeast 10, 14. Yeast Ipk2/Ipmk/IP3K is a dual-specificity IP3/IP4 6/3-kinase and identical to Arg82/ArgRIII which is an indispensable component of ArgR-Mcm1 transcriptional complex 10. The ArgR-Mcm1 complex functions in transcriptional control of genes involved in arginine metabolism 32, 33. However, the inositol phosphorylation activity Arg82 is not required for the transcriptional regulation 34. We previously reported the molecular cloning and characterization of a plant IP3K gene (AtIpk2β/AtIP3K) from Arabidopsis 15. The amino acid sequence of AtIpk2β shares 73% identity and 84% similarity to that of a second Arabidopsis IP3K, AtIpk2α. 15, 35. Similar to yeast IP3K, Arabidopsis IP3K is also a dual-specificity 6/3-kinase 15, 35. York and his colleagues reported that Arabidopsis IP3K has a novel 5-kinase activity to phosphate I(1,3,4,6)P4 to generate I(1,2,3,4,6)P5 35. Identified Ipmks include those from human 36 and rat 37.
Human Ipmk is very similar to rat Ipmk with 84% amino acid sequence identity 31. Arabidopsis IP3K and yeast IP3K are less conserved in the Ipmk superfamily with 25% and 16% amino acid sequence identity to human Ipmk respectively 31. Within the catalytic domain of Ipmks family, mammalian homologues share 25-33% and 42-54% identity to yeast and Arabidopsis IP3Ks respectively. Ipmks have conserved IP-binding consensus sequence and ATP-binding site in their catalytic domain 31. Fig. 2 depicts a schematic alignment of IP3Ks from rat, human, yeast and Arabidopsis. The expression patterns of Ipmks are different: rat Ipmk is highly expressed in kidney and brain 37, whereas human Ipmk is ubiquitously expressed 36. Although Arabidopsis IP3K has similar transcript level in flower, root, stem, and leave 15, its activity is detected only in mature pollens, but not in immature pollen grains 15.
IP3K STRUCTURE
There are two major functional domains in mammalian IP3Ks: a highly conserved C-terminal catalytic domain and a divergent N-terminal regulatory domain. The structure of mammalian IP3Ks catalytic core (residues 185-459 of rat RnIP33K-A) consists of two domains: a large α/β-class structure and a small α-helical structure 38, 39, 40. The α/β-class structure has two lobes that are necessary for ATP/Mg2+-binding with critical residues Lys-197, Lys-262, Arg-317 and Asp-414, whereas the small α-helical structure is responsible for IP3-binding in dependence of a 35 amino acid sequence of Arg-276 to Lys-303 39, 40, 41, 42, 43. Many hydrophobic residues of the large domain also participate in ATP binding 39. The IP3-binding core is inserted between two lobes of the large domain acting together during ATP binding and phosphate transfer 43, 44. Sequence alignment of IP3Ks shows that consensus sequence PxxxDxKxG is a highly conserved motif for substrate binding 31. However, the small helix domain is absent in mammalian Ipmks, yeast and Arabidopsis IP3Ks 39. This may explain the substrate specificity of IP3 3-kinase and Ipmk from the structure level. Motif [L/M][I/V]D[F/L][A/G][H/K] is also considered as a putative ATP/Mg2+-binding sequence in Ipmks 37. Furthermore Saiardi et al identified a new domain designated “SSLL” in rat Ipmk 37. The SSLL-like motif is also conserved within other IP3Ks 31, 37. Mutational analysis shows that loss of this motif may impair catalysis activity of IP3Ks 37.
Intracellular localization of IP3Ks is contributed by special domains. A novel N-terminal 66 amino acid sequence in rat RnIP33K-A is involved in F-actin binding 45. A similar actin-binding domain was also identified in rat RnIP33K-B 46. Rat RnIP33K-B can bind to ER membrane with high-affinity, depending upon conformation, and protein-protein interaction 30. Soriano and Banting hypothesized that the N-terminus of RnIP33K-B was only required for the binding of the enzyme to the ER in proximity of the IP3 receptor 30. This N-terminal 320 amino acids are unique for the rat IP3K isoform B, which contributes to its subcellular localization to the ER 30. Rat RnIP33K-C is exclusively cytoplasmic but shuttles between cytoplasm and the nucleus 23. A nuclear export signal (NES) has been identified at its N-terminus 23. A similar nuclear localization signal (NLS) has also been discovered in human Ipmk 47. Both yeast and Arabidopsis IP3Ks are nucleus localized 10, 15. However, no obvious NSL can be found through sequence alignment 15. Different domains are presented in Fig. 2.
IP3K REGULATORS
Ca2+/CaM
Mammalian IP3Ks can be activated by CaM in a Ca2+-dependent manner to different degrees. CaM recognizes sequences which contain amphiphilic α-helices with clusters of positively charged and hydrophobic amino acids 38. Sequence from Ser-156 to Leu-189 together with site Trp-165 in rat IP33K-A is required for CaM binding and the enzyme activation 38, 48, 49. The level of stimulation appears to be cell-, tissue- and isoform-specific 27, 50 (Tab. 1). Up to 20-fold of increase in IP3Ks enzymatic activities by Ca2+/CaM can be observed in a in vitro assay using purified IP3Ks from rat 17, 51, pig and human 29, 52, 53. However, IP3Ks from nematode 25, Arabidopsis 15 and yeast 10 lack the consensus CaM-binding sites and thus are insensitive to Ca2+/CaM.
PKA, PKC and CaMKII
Mammalian IP3Ks are substrates of camp-dependent kinase (PKA), protein kinase C (PKC) and Ca2+/CaM-denpendent kinase II (CaMKII). PKA can stimulate IP3K activity. In contrast, PKC is a negative regulator of IP3K 54. Ser-175 on RnIP33K-A is the phosphorylation site for PKC, and Ser-109 for both PKC and PKA 28. Simultaneous phosphorylation of Ser-109 and Ser-175 leads to inactivation of the enzyme, whereas a single phosphorylation at Ser-109 activates it, suggesting that Ser-175 is probably the inhibitory phosphorylation site 28. CaMKII is also a positive regulator of IP3K 55. Thr-311 of human HsIP33K-A is a CaMKII phosphorylation site. CaMKII can stimulate enzyme activity by 8~10-fold 54, 55. The phosphorylation level of IP3K varies depending upon Ca2+/CaM-sensitivity and different isoforms 55. To date, it is not clear whether Ipmk is sensitive to PKC, PKA, CaMKII. But Arabidopsis IP3K can be phosphorylated by PKC in vitro 15. Further experiments are needed to elucidate how the activity of Arabidopsis IP3K is regulated.
Other regulators
Mammalian IP3Ks activity can be stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) in the presence of cAMP 56, 57, 58. Protein stability is also involved such as mammalian IP3Ks are very sensitive to calpains 59. Pp60v-src kinase can also increase IP3K activity, although the src-phosphorylation site in IP3K has not been identified yet 60.
IP3K FUNCTIONS
IP3Ks are involved in inositol signaling pathway, calcium signal transduction, brain development, stress responses and gene transcription (Fig. 3).
Inositol signaling pathway
Mammalian IP3Ks mainly phosphorylate IP3 to IP4 to provide precursors for synthesis of higher IPs 5, 31. Yeast and Arabidopsis IP3Ks participate additional pathway in IP metabolism 10, 15. In yeast, there is a subdivision of lipid-dependent pathway for IP6 synthesis 10. IP3K phosphorylates IP3 stepwise at the D-6 and D-3 positions to generate IP5 or as a minor pathway to phosphorylate IP3 to bring about IP4 10, 14. There is evidence showing that expansion of an IP3 pool could lead to increases of IP4, IP5 and IP6 levels via Ipmk 61. Thus, in higher eukaryotes Ipmk, but not IP3 3-kinase, may be the main contributor for IP5 and IP6 syntheses 61. Plant react in a similar way. Maize IP3K (ZmIpk) is responsible for IP6 biosynthesis in developing maize seed 62. Arabidopsis IP3K has 6-/3-kinase activity and can phosphorylate IP3 to give rise to IP5 15, 35. Besides, Arabidopsis IP3K exhibits a novel 5-kinase activity to produce IP5 from I(1,3,4,6)P4 35. The 5-kinase activity has also been detected in human and Drosophila Ipmks 36, 61, which is especially important for fruit flies since no IP3 5-/6-kinase can be found in this animal. Human Ipmk can also phosphorylate inositol 4,5-biphosphate (IP2) to generate to IP3 and can make pyrophosphate disphosphoinositol tetrakisphosphate (PP-IP4) from IP5 36.
Calcium signal transduction
IP3 and IP4 regulate Ca2+ mobilization synergistically 2, 4. Increase of IP3K activity may reduce cellular IP3 concentration and correspondingly terminate IP3 action. The function of IP4 is implicated in promoting Ca2+ entry from extracellular space 4. Evidence shows that IP4 can activate a protein with ras- and rap-GAP activity and finally inactivate the G protein 30. This indicates that IP4 regulates Ca2+ influx in a GTP-dependent way, which potentially links the IP3 signaling pathway to GTP-regulated signaling mechanisms 30. IP4 is demonstrated to be a common regulator in Ca2+ homeostasis 63. A complete inhibition of IP3K activity in Hela cells by adriamycin or by IP3K-specific antibody blocked Ca2+ oscillations, whereas a partial inhibition caused a significant reduction in oscillations frequency 63. Taken together, IP3K activity is related to the levels of IP3 and IP4 and subsequently to Ca2+ oscillations (Fig. 3). However, it remains unknown whether yeast and Arabidopsis IP3Ks are involved in regulation of Ca2+ oscillations. Recombinant yeast IP3K mainly phosphorylates IP3 to give rise I(1,4,5,6)P4 10, 35. However, I(1,4,5,6)P4 is not as efficient as IP4 in Ca2+ influx. Yeast IP3K thus may not be relevant to Ca2+ oscillations in vivo.
Brain development, memory and learning
Rat and human IP3Ks may be involved in brain development, memory and learning. Rat IP3K activity is low at birth and reaches approximately 50% of adult levels 64. Rat IP3K activities are the highest in the hippocampal CA1 pyramidal neurons, dentate gyrus granule cells, and cerebellar purkinje cells 64, 65. On the other hand, low activities were found in cerebellar granule cells, thalamus, hypothalamus, brainstem, spinal cord, and white matter tracts 64, 65. The expression pattern of human HsIP33K-A is similar to that of rat RnIP33K-A. Human HsIP33K-B is predominantly present in astrocytes 66, 67. The distribution of IP3Ks in rat and human brain suggests that IP3K might be involved in brain development and in memory process 68. Spatial learning training leads to the increase of rat RnIP33K-A level , suggesting a possible role of rat RnIP33K-A in spatial learning 69.
Stress responses
Interestingly, a Drosophila IP3K gene (D-IP3K1) appears to be oxidative damage resistant 26. Ubiquitous over-expression of D-IP3K1 confers resistance of flies to H2O2- but not to paraquat-induced oxidative stress 26. Evidence suggests that the protective effect of D-IP3K1 is mainly due to a reduced IP3 level and thus reduced calcium release from internal stores, rather than an increased IP4 level 26. IP3K activity is the key player in this process 26. In yeast, the IP3K activity has also been demonstrated to be required for resistance to salt stress, cell wall integrity and vacuolar morphogenesis 70.
Gene transcription
Yeast IP3K (Ipk2/Arg82) was identified as a regulator of arginine metabonism 10. The complex ArgR-Mcm1 is required to ensure the coordination of gene expression in response to arginine 10, 71. Arg80 and Mcm1 are members of the MADS-box transcription factor family, whereas Arg81, a zinc cluster protein, is the sensor of arginine 72. Three components (Arg80, Arg81 and Mcm1) are sufficient to form a complex with DNA (arginine boxes) in the presence of arginine 72. Yeast IP3K stabilizes Mcm1 and Arg80, and facilitates their assembly into a multimeric complex 72. A poly-Asp domain within amino acid residues 282-303 of yeast IP3K is essential for stability of Arg80 and Mcm1 73. It was argued that the absence of this domain leads to the failure of forming ArgR-Mcm1 transcriptional complex 73. Arabidopsis IP3K has a similar function, which complements yeast Arg82/Ipk2 mutant lacking a functional ArgR-Mcm1 transcriptional complex 15. However, no significant poly-Asp domain is found in Arabidopsis IP3K 15. This evidence is somewhat contradicted to previous hypothesis about the role of yeast IP3K in forming transcriptional complex.
Others
IP4 can bind with high affinity to several intracellular proteins—synaptotagmin (I and II), Gap1, Btk, and centaurin-α—and may interact with synaptotagmin to inhibit synaptic transmission 74. IP4 also acts as a mediator in neuronal death in the ischemic hippocampus 75. The changes in IP3 metabolism may be correlated to critical stages of muscle development and differentiation, which suggests a possible role for IP3K in these processes 76. Moreover, yeast IP3K is involved in cellular mRNA export from the nucleus with Ipk1 and plays a role in determining messenger RNA export from yeast nucleus 10, 77. Recent analysis shows that Arabidopsis IP3K (AtIpk2α) is also associated with pollen germination and root growth 78.
PERSPECTIVE
Signaling crosstalk
IP3K may be a key player in integrating Ca2+ signaling, IP metabolism and other signaling pathways. In plant, Ca2+ levels are modulated by IP3 in response to various signals including hormones, light and abiotic stresses. For example, the addition of abscisic acid (ABA) leads to increase in endogenous IP3 levels 79; red light elicits a rapid Ca2+ intracellular release which can be mimicked by microinjection of IP3 80; gravity stimulates a rapid increase of IP3 in maize 81. However, this may not be the only way for IP3K function in many biological processes. IP4, IP5, and IP6 have been demonstrated functionally important 9, 10, 11, 12, 13, 82. They have recently been implicated as messengers regulating cellular processes including transcription, DNA repair and channel activity 6, 7. IP6 serves as a storage poll of IPs and mineral nutrients in seeds 12, 13. Thus, IP3K may also participate in controlling plant development by regulating subsequent IP signaling pathways. A new exciting function for yeast and Arabidopsis IP3Ks was found in regulation of gene expression 10, 15. A fully understand of the physiological function of IP3K needs a comprehensive consideration of IP3K network. IP3K may simultaneously regulate Ca2+ homeostasis, IP metabolism and gene transcription in response to external stimulus.
Inositol phosphate metabolism
Signals induced by IP3 can be terminated by two ways; either through dephosphorylation by a 5- phosphatase to give inositol 1,4-biphosphate (IP2) or through phosphorylation by IP3K to produce IP4 83. Ipmk may replace IP33-kinase due to their similar enzymatic activities 10, 35. Cellular IP3 serves as a substrate for both IP3 3-kinase and Ipmk to form IP6 61. Ipmk, but not IP33-kinase, is the major enzyme in IP6 synthesis, whereas IP33-kinase mainly function in IP4 synthesis from IP3 61. Different from animal homologues, only two IP3K isoforms (AtIpk2α and AtIpk2β) were isolated from Arabidopsis 15, 35. The general pathway for IP6 synthesis in plant as well as in yeast has been identified as follow: IP3→IP4/I(1,4,5,6)P4→IP5→IP6 35. The first two steps can be phosphorylated by yeast and plant IP3Ks 10, 15, 35. But 3-kinase activity of yeast and Arabidopsis IP3Ks seems less active than their in vivo 6-kinase activity 10, 35. Thus, of particular interest is the mechanism of regulating Ca2+ release and influx in plant cells. However, Arabidopsis IP3K regulating pollen tube growth under different environmental conditions is Ca2+-independent 78.
Gene transcriptional control
The crystal structure of Ipmk is not yet known. Information from mammalian IP3K catalytic domain suggests that yeast and Arabidopsis IP3Ks may interact with other molecules 39, 40. Sun et al copurified COP9 signalsome/CSN from calf brain with inositol 1,3,4-trisphosphate 5/6-kinase 84. This kinase can phosphorylate several transcription factors (NF-κB, c-Jun, p53 etc,) to avoid of degradation by the ubiquitin system 84. Both NF-κB and c-Jun play important roles in brain development and anti-oxidative stress 85, 86. Yeast IP3K activates ArgR-Mcm1 complex and then drives transcription 31. We have also demonstrated that Arabidopsis IP3K complemented ipk2 mutant yeast 15, indicating a potential function of Arabidopsis IP3K in transcription regulation.
IP3K regulation
Mammalian IP3Ks can be modulated by Ca2+/CaM, PKA, PKC, CaMKII and other regulators. However, there is little information about the mechanism. Both yeast and Arabidopsis IP3Ks lack CaM-binding sites and are insensitive to Ca2+/CaM 10, 15. Therefore, compared to mammalian IP3Ks, they are most regulated by different mechanisms. Our preliminary experiments suggest that Arabidopsis IP3K can be phosphorylated by PKC in vitro. Whether such phosphorylation is physiologically relevant to the regulation of Arabidopsis IP3K activity in vivo is not clear. It is important to understand the function regulation of yeast and plant IP3Ks in the near future.
References
Carafoli E . Calcium signaling: a tale for all seasons. Proc Natl Acad Sci USA 2002; 99:1115–22.
Irvine RF . Inositol phosphates and Ca2+ entry-towards a proliferation, or a simplification? ASEB J 1992; 6:3085–91.
Vetter SW, Leclerc E . Novel aspects of calmodulin target recognition and activation. Eur J Biochem 2003; 270:404–14.
Mignery GA, Johnston PA, Sudhof TC . Mechanism of Ca2+ inhibition of inositol 1,4,5-trisphosphate (InsP3) binding to the cerebellar InsP3 receptor. J Biol Chem 1992; 267:7450–5.
Berridge MJ . Inositol and calcium signalling. Nature 1993; 361:315–25.
Majerus PW . Inositol phosphate biochemistry. Annu Rev Biochem 1992; 61:225–50.
Irvine RF, Schell MJ . Back in the water: the return of the inositol phosphates. Nat Rev Mol Cell Biol 2001; 2:327–38.
Cullen PJ, Hsuan JJ, Truong O, et al. Identification of a specific Ins(1,3,4,5)P4-binding protein as a member of the GAP1 family. Nature 1995; 376:527–30.
Ferry S, Matsuda M, Yoshida H, Hirata M . Inositol hexa-kisphosphate blocks tumor cell growth by activating apoptotic machinery as well as by inhibiting the Akt/NF-κb mediated cell survival pathway. Carcinogenesis 2002; 23:2031–41.
Odom AR, Stahlberg A, Wente SR, York JD . A role for nuclear inositol 1,4,5-trisphosphate kinase in transcriptional control. Science 2000; 287:2026–9.
Eggleton P, Penhallow J, Crawford N . Priming action of inositol hexakisphosphate (InsP6) on the stimulated respiratory burst in human neutrophils. Biochim Biophys Acta 1991; 1094:309–16.
Raboy V, Gerbasi P . Genetics of myo-inositol phosphate synthesis and accumulation. Subcell Biochem 1996; 26:257–85.
Loewus FA, Murthy PPN . myo-Inositol metabolism in plants. Plant Sci 2000; 150:1–19.
Saiardi A, Erdjument-Bromage H, Snowman A, Tempst P, Snyder SH . Synthesis of diphosphoinositol pentakisphosphate by a newly identified family of higher inositol polyphosphate kinase. Curr Biol 1999; 9:23–1326.
Xia HJ, Brearley C, Elge S, et al. Arabidopsis inositol polyphosphate 6-/3-kinase is a nuclear protein that complements a yeast mutant lacking a functional ArgR-Mcm1 transcription complex. Plant Cell 2003; 15:449–63.
Choi KY, Kim HK, Lee SY, Moon KH, Sim SS, Kim JW, Chung HK, Rhee SG . Molecular cloning and expression of a complementary DNA for inositol 1,4,5-trisphosphate 3-kinase. Science 1990; 248:64–6.
Takazawa K, Lemos M, Delvaux A, et al. Rat brain inositol 1,4,5-trisphosphate 3-kinase. Ca2+-sensitivity, purification and antibody production. Biochem J 1990; 268:213–7.
Takazawa K, Vandekerckhove J, Dumont JE, Erneux C . Cloning and expression in Escherichia coli of a rat brain cDNA encoding a Ca2+/calmodulin-sensitive inositol 1,4,5-trisphosphate 3-kinase. Biochem J 1990; 272:107–12.
Takazawa K, Perret J, Dumont JE, Erneux C . Molecular cloning and expression of a new putative inositol 1,4,5-trisphosphate 3-kinase isoenzyme. Biochem J 1991; 278:883–6.
Takazawa K, Perret J, Dumont JE, Erneux C . Molecular cloning and expression of a human brain inositol 1,4,5-trisphosphate 3-kinase. Biochem Biophys Res Commun 1991; 174:529–535.
Thomas S, Brake B, Luzio JP, Stanley K, Banting G . Isolation and sequence of a full-length cDNA encoding a novel rat inositol 1,4,5-trisphosphate 3-kinase. Biochim Biophys Acta 1994; 1220:219–22.
Dewaste V, Pouillon V, Moreau C, et al. Cloning and expression of a cDNA encoding human inositol 1,4,5-trisphosphate 3-kinase C. Biochem J 2000; 352:343–51.
Nalaskowski MM, Bertsch U, Fanick W, et al. Rat inositol 1,4,5-trisphosphate 3-kinase C is enzymatically specialized for basal cellular inositol trisphosphate phosphorylation and shuttles actively between nucleus and cytoplasm. J Biol Chem 2003; 278:19765–76.
Bertsch U, Haefs M, Möller M, et al. A novel A-isoform-like inositol 1,4,5-trisphosphate 3-kinase from chicken erythrocytes exhibits alternative splicing and conservation of intron positions between vertebrates and invertebrates. Gene 1999; 228:61–71.
Clandinin TR, DeModena JA, Sternberg PW . Inositol trisphosphate mediates a RAS-independent response to LET-23 receptor tyrosine kinase activation in C. elegans. Cell 1998; 92:523–33.
Monnier V, Girardot F, Audin W, Tricoire H . Control of oxidative stress resistance by IP3 kinase in Drosophila melanogaster. Free Radic Biol Med 2002; 33:1250–9.
Dewaste V, Moreau C, De Smedt F, et al. The three isoenzymes of human inositol-1,4,5-trisphosphate 3-kinase show specific intracellular localization but comparable Ca2+ responses on transfection in COS-7 cells. Biochem J 2003; 374:41–9.
Sim SS, Kim JW, Rhee SG . Regulation of D-myo-inositol 1,4,5-trisphosphate 3-kinase by cAMP- dependent protein kinase and protein kinase C. J Biol Chem 1990; 265:10367–72.
Vanweyenberg V, Communi D, D'Santos CS, Erneux C . Tissue- and cell-specific expression of Ins(1,4,5)P3 3-kinase isoenzymes. Biochem J 1995; 306:429–35.
Soriano S, Banting G . Possible roles of inositol 1,4,5-trisphosphate 3-kinase B in calcium homeostasis. FEBS lett 1997; 403:1–4.
Shears SB . How versatile are inositol phosphate kinases? Biochem J 2004; 377:265–80.
Dubois E, Messenguy F . Pleiotropic function of ArgRIIIp (Arg82p), one of the regulators of arginine metabolism in Saccharomyces cerevisiae. Role in expression of cell-type-specific genes. Mol Gen Genet 1994; 243:315–24.
Bercy J, Bubios E, Messenguy F . Regulation of arginine metabolism in Saccharomyces cerevisiae: expression of three ARGR regulatory genes. Gene 1987; 55:277–85.
Dubois E, Dewaste V, Erneux C, Messenguy F . Inositol polyphosphate kinase activity of Arg82/ArgRIII is not required for the regulation of the arginine metabolism in yeast. FEBS Lett 2000; 486:300–4.
Stevenson-Paulik J, Odom AR, York JD . Molecular and biochemical characterization of two plant inositol polyphosphate 6-/3-/5-kinases. J Biol Chem 2002; 277:42711–8.
Chang SC, Miller AL, Feng Y, Wente SR, Majerus PW . The human homolog of the rat inositol phosphate multikinase is an inositol 1,3,4,6-tetrakisphosphate 5-kinase. J Biol Chem 2002; 277:43836–43.
Saiardi A, Nagata E, Luo HR, et al. Mammalian inositol polyphosphate multikinase synthesizes inositol 1,4,5-trisphosphate and an inositol pyrophosphate. Proc Natl Acad Sci USA 2001; 98:2306–11.
Takazawa K, Erneux C . Identification of residues essential for catalysis and binding of calmodulin in rat brain inositol 1,4,5-trisphosphate 3-kinase. Biochem J 1991; 280:125–9.
Miller GJ, Hurley JH . Crystal structure of the catalytic core of inositol 1,4,5-trisphosphate 3-kinase. Mol Cell 2004; 15:703–11.
Gonzalez B, Schell MJ, Letcher A, et al. Structure of a human inositol 1,4,5-trisphosphate 3-kinase: substrate binding reveals why it is not a phosphoinositide 3-kinase. Mol Cell 2004; 15:689–701.
Communi D, Takazawa K, Erneux C . Lys-197 and Asp-414 are critical residues for binding of ATP/Mg2+ by rat brain inositol 1,4,5-trisphosphate 3-kinase. Biochem J 1993; 291:811–6.
Communi D, Lecocq R, Vanweyenberg V, Erneux C . Active site labeling of inositol 1,4,5-trisphosphate 3-kinase A by phenylglyoxal. Biochem J 1995; 310:109–15.
Togashi S, Takazawa K, Endo T, Erneux C, Onaya T . Structural identification of the myo-inositol 1,4,5-trisphosphate-binding domain in rat brain inositol 1,4,5-trisphosphate 3-kinase. Biochem J 1997; 326:221–5.
Bertsch U, Deschermeier C, Fanick W, et al. The second messenger binding site of inositol 1,4,5-trisphosphate 3-kinase is centered in the catalytic domain and related to the inositol trisphosphate receptor site. J Biol Chem 2000; 275:1557–64.
Schell MJ, Erneux C, Irvine RF . Inositol 1,4,5-trisphosphate 3-kinase associates with F-actin and dendritic spines via its N terminus. J Biol Chem 2001; 276:37537–46.
Brehm MA, Schreiber I, Bertsch U, Wegner A, Mayr GW . Identification of the actin-binding domain of Ins(1,4,5)P3 3-kinase isoform B (IP3K-B). Biochem J 2004; 382:353–62.
Nalaskowski MM, Deschemeier C, Fanick W, Mayr G W . The human homologue of yeast ArgRIII is an inositol phosphate multikinase with predominantly nuclear localization. Biochem J 2002; 266:549–56.
Erneux C, Moreau C, Vandermeers A, Takazawa K . Interaction of calmodulin with a putative calmodulin-binding domain of inositol 1,4,5-trisphosphate 3-kinase. Effects of synthetic peptides and site-directed mutagenesis of Trp165. Eur J Biochem 1993; 214:497–501.
Yamaguchi K, Hirata M, Kuriyama H . Calmodulin activates inositol 1,4,5-trisphosphate 3-kinase activity in pig aortic smooth muscle. Biochem J 1987; 244:787–91.
Dewaste V, Roymans D, Moreau C, Erneux C . Cloning and expression of a full-length cDNA encoding human inositol 1,4,5-trisphosphate 3-kinase B. Biochem Biophys Res Commun 2002; 291:400–5.
Conigrave A, Patwardhan A, Broomhead L, Roufogalis B . A purification strategy for inositol 1,4,5-trisphosphate 3-kinase from rat liver based upon heparin interaction chromatography. Cell Signal 1992; 4:303–12.
Lin A, Wallace RW, Barnes S . Purification and properties of a human platelet inositol 1,4,5-trisphosphate 3-kinase. Arch Biochem Biophys 1993; 303:412–20.
Woodring PJ and James C. Garrison . Expression, purification, and regulation of two isoforms of the inositol 1,4,5-trisphosphate 3-kinase. J Biol Chem 1997; 272:30447–54.
Lin AN, Barnes S, Wallace RW . Phosphorylation by protein kinase C inactivates an inositol 1,4,5-trisphosphate 3-kinase purified from human platelets. Biochem Biophys Res Commun 1990; 170:1371–6.
Communi D, Vanweyenberg V, Erneux C . D-myo-inositol 1,4,5-trisphosphate 3-kinase A is activated by receptor activation through a calcium: calmodulin-dependent protein kinase II phosphorylation mechanism. Embo J 1997; 16:1943–52.
Biden TJ, Wollheim CB . Ca2+ regulates the inositol tris/tetrakisphosphate pathway in intact and broken preparations of insulin-secreting RINm5F cells. J Biol Chem 1986; 261:11931–4.
Biden TJ, Altin JG, Karjalainen A, Bygrave FL . Stimulation of hepatic inositol 1,4,5-trisphosphate kinase activity by Ca2+-dependent and -independent mechanisms. Biochem J 1988; 256:697–701.
Imboden JB, Pattison G . Regulation of inositol 1,4,5-trisphosphate kinase activity after stimulation of human T cell antigen receptor. J Clin Invest 1987; 79:1538–41.
Lee SY, Sim SS, Kim JW, et al. Purification and properties of D-myo-inositol 1,4,5-trisphosphate 3- kinase from rat brain. Susceptibility to calpain. J Biol Chem 1990; 265:9434–40.
Johnson RM, Wasilenko WJ, Mattingly RR, Weber MJ, Garrison JC . Fibroblasts transformed with v-src show enhanced formation of an inositol tetrakisphosphate. Science 1989; 246:121–4.
Seeds AM, Sandquist JC, Spana ER, York JD . A molecular basis for inositol polyphosphate synthesis in Drosophila melanogaster. J Biol Chem 2004; 279:47222–32.
Shi J, Wang H, Wu Y, Hazebroek J, et al. The maize low-phytic acid mutant lpa2 is caused by mutation in an inositol phosphate kinase gene. Plant Physiol 2003; 131:507–15.
Zhu DM, Tekle E, Huang CY, Chock PB . Inositol tetrakisphosphate as a frequency regulator in calcium oscillations in HeLa cells. J Biol Chem 2000; 275:6063–6.
Mailleux P, Takazawa K, Erneux C, Vanderhaeghen JJ . Inositol 1,4,5-trisphosphate 3-kinase mRNA: high levels in the rat hippocampal CA1 pyramidal and dentate gyrus granule cells and in cerebellar Purkinje cells. J Neurochem 1991; 56:345–7.
Heacock AM, Seguin EB, Agranoff BW . Developmental and regional studies of the metabolism of inositol 1,4,5-trisphosphate in rat brain. J Neurochem 1990; 54:1405–11.
Mailleux P, Takazawa K, Albala N, Erneux C, Vanderhaeghen JJ . Comparison of neuronal inositol 1,4,5-trisphosphate 3-kinase and receptor mRNA distributions in the human brain using in situ hybridization histochemistry. Neurosci Lett 1992; 137:69–71.
Mailleux P, Takazawa K, Albala N, Erneux C, Vanderhaeghen JJ . Astrocytic localization of the messenger RNA encoding the isoenzyme B of inositol (1,4,5)P3 3-kinase in the human brain. Neurosci Lett 1992; 148:177–80.
Mailleux P, Takazawa K, Erneux C, Vanderhaeghen JJ . Inositol 1,4,5-trisphosphate 3-kinase distribution in the rat brain. High levels in the hippocampal CA1 pyramidal and cerebellar Purkinje cells suggest its involvement in some memory processes. Brain Res 1991; 539:203–10.
Kim IH, Park SK, Sun W, et al. Spatial learning enhances the expression of inositol 1,4,5-trisphosphate 3-kinase A in the hippocampal formation of rat. Brain Res Mol Brain Res 2004; 124:12–9.
Dubois E, Scherens B, Vierendeels F, et al. In Saccharomyces cerevisiae, the inositol polyphosphate kinase activity, and vacuolar morphogenesis. J Biol Chem 2002; 277:23755–63.
York JD, Odom AR, Murphy R, Ives EB, Wente SR . A phospholipase C-dependent inositol polyphosphate kinase pathway required for efficient messenger RNA export. Science 1999; 285:96–100.
El Alami M, Messenguy F, Scherens B, Dubois E . Arg82p is a bifunctional protein whose inositol phosphate kinase activity is essential for nitrogen and PHO gene expression but not for Mcm1p chaperoning in yeast. Mol Microbiol 2003; 49:457–68.
Saiardi A, Caffrey JJ, Snyder SH, Shears SB . Inositol polyphosphate multikinase (ArgRIII) determines nuclear mRNA export in Saccharomyces cerevisiae. FEBS Lett 2000; 468:28–32.
Sims CE, Nancy L . Allbritton metabolism of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate by the oocytes of Xenopus laevis. J Biol Chem 1998; 273:4052–8.
Tsubokawa H, Oguro K, Robinson HP, et al. Inositol 1,3,4,5-tetrakisphosphate as a mediator of neuronal death in ischemic hippocampus. Neuroscience 1994; 59:291–7.
Carrasco MA, Marambio P, Jaimovich E . Changes in IP3 metabolism during skeletal muscle development in vivo and in vitro. Comp Biochem Physiol B Biochem Mol Bio 1997; 116:173–81.
Amar N, Messenguy F, Bakkoury ME, Dubois E . ArgRII, a component of the ArgR-Mcm1 complex involved in the control of arginine metabolism in Saccharomyces cerevisiae, is the sensor of Arginine. Mol Cell Biol 2000; 20:2087–97.
Xu J, Brearley CA, Lin WH, et al. A role of Arabidopsis inositol polyphosphate kinase AtIpk2α, in pollen germination and root growth. Plant Physiol 2005; 137:94–103.
Lee Y, Choi Y, Suh S, et al. Abscisic acid-induced phosphoinositide turnover in guard cell protoplasts of Vicia faba. Plant Physiol 1996; 110:987–96.
Shacklock PS, Read ND, Trewavas AJ . Cytosolic free calcium mediates red light-induced photomorphogenesis. Nature 1992; 358:753–55.
Perera IY, Heilmann I, Boss WF . Transient and sustained increases in inositol 1,4,5-trisphosphate precede the differential growth response in gravistimulated Maize pulvini. Proc Natl Acad Sci USA 1999; 96:5838–43.
Pouillon V, Hascakova-Bartova R, Pajak B, et al. Inositol 1,3,4,5-tetrakisphosphate is essential for T lymphocyte development. Nat Immunol 2003; 4:1136–43.
Erneux C, Govaerts C, Communi D, Pesesse X . The diversity and possible functions of the inositol 5-polyphosphatases. Biochim Biophys Acta 1998; 1436:185–99.
Sun Y, Wilson MP, Majerus PW . Inositol 1,3,4-Trisphosphate 5/6-Kinase Associates with the COP9 Signalosome by Binding to CSN1. J Bio Chem 2002; 277:45759–64.
Hiscott J, Kwon H, Génin P . Hostile takeovers: viral appropriation of the NF-κB pathway. J Clin Invest 2001; 107:143–51.
Rodríguez-Iturbe B, Vaziri ND, Herrera-Acosta J, Johnson RJ . Oxidative stress, renal infiltration of immune cells, and salt-sensitive hypertension: all for one and one for all. Am J Physiol Renal Physiol 2004; 286:606–16.
El Backkoury M, Dubois E, Messenguy F . Recruiment of yeast MADS-box proteins, ArgRI and Mcm1 by the pleitropic factor ArgRIII is required for their stability. Mol Microbiol 2000; 35:15–31.
Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (No. 30370142), the National Special Key Project on Functional Genomics and Biochip of China (No. 2002AA2Z1002) and the Project sponsored by the Scientific Research Foundation for the Returned Oversea Chinese Scholars, State Education Ministry. We thank Dr. Yun-Bo Shi, Dr. Bernd Mueller-Roeber, Dr. Jian-Kang Zhu and Dr. Hao Yu for their critical readings of this manuscript.
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XIA, H., YANG, G. Inositol 1,4,5-trisphosphate 3-kinases: functions and regulations. Cell Res 15, 83–91 (2005). https://doi.org/10.1038/sj.cr.7290270
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DOI: https://doi.org/10.1038/sj.cr.7290270
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