Inositol Pentakisphosphate Mediates Wnt/β-Catenin Signaling

Gao, Yuan; Wang, Hsien‐yu

doi:10.1074/jbc.m702106200

Cited by 48 publications

(57 citation statements)

References 61 publications

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“…Journal of Cell Science 121 (21) activity (Gao and Wang, 2007). The nature of signaling intermediates between p38 MAPK and GSK3β inactivation awaits further study.…”

Section: Discussionmentioning

confidence: 99%

p38 mitogen-activated protein kinase regulates canonical Wnt–β-catenin signaling by inactivation of GSK3β

Bikkavilli

Feigin

Malbon

2008

Journal of Cell Science

169

128

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“…Journal of Cell Science 121 (21) activity (Gao and Wang, 2007). The nature of signaling intermediates between p38 MAPK and GSK3β inactivation awaits further study.…”

Section: Discussionmentioning

confidence: 99%

p38 mitogen-activated protein kinase regulates canonical Wnt–β-catenin signaling by inactivation of GSK3β

Bikkavilli

Feigin

Malbon

2008

Journal of Cell Science

169

128

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“…Derivatives of m-Ins, and phosphatidylinositol derivatives, in particular, have an established role in Wnt-mediated pathways of embryo development (including zebrafish). 25,26 Wnt pathways are a well-described group of signal transduction pathways that regulate crucial aspects of cell-fate determination, cell migration, cell polarity, morphological patterning, and organogenesis during embryonic development. Phosphatidylinositol-based signaling is recognized to serve as a key intracellular function in this regard.…”

Section: Discussionmentioning

confidence: 99%

High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance of Intact Zebrafish Embryos Detects Metabolic Changes Following Exposure to Teratogenic Polymethoxyalkenes from Algae

et al. 2016

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Techniques based on nuclear magnetic resonance (NMR) for imaging and chemical analyses of in vivo, or otherwise intact, biological systems are rapidly emerging and finding diverse applications within a wide range of fields. Very recently, several NMR-based techniques have been developed for the zebrafish as a model animal system. In the current study, the novel application of high-resolution magic angle spinning (HR-MAS) NMR is presented as a means of metabolic profiling of intact zebrafish embryos. Toward investigating the utility of HR-MAS NMR as a toxicological tool, these studies specifically examined metabolic changes of embryos exposed to polymethoxy-1-alkenes (PMAs)-a recently identified family of teratogenic compounds from freshwater algae-as emerging environmental contaminants. One-dimensional and two-dimensional HR-MAS NMR analyses were able to effectively identify and quantify diverse metabolites in early-stage (£36 h postfertilization) embryos. Subsequent comparison of the metabolic profiles between PMA-exposed and control embryos identified several statistically significant metabolic changes associated with subacute exposure to the teratogen, including (1) elevated inositol as a recognized component of signaling pathways involved in embryo development; (2) increases in several metabolites, including inositol, phosphoryl choline, fatty acids, and cholesterol, which are associated with lipid composition of cell membranes; (3) concomitant increase in glucose and decrease in lactate; and (4) decreases in several biochemically related metabolites associated with central nervous system development and function, including c-aminobutyric acid, glycine, glutamate, and glutamine. A potentially unifying model/hypothesis of PMA teratogenicity based on the data is presented. These findings, taken together, demonstrate that HR-MAS NMR is a promising tool for metabolic profiling in the zebrafish embryo, including toxicological applications.

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“…Nonetheless, our data linking changes in this putative IP code to G protein activation in mammals provide an impetus to explore whether agonist stimulation of any of the hundreds of GPCR or possibly even the RTK pathways alters the code and whether one or more of the IPK gene products is required to mediate signaling processes. Of particular relevance, during the revision of this manuscript, Gao et al (35) found that Wnt3a activation of G␣ q (through the Frizzled-1 receptor) causes a transient increase in IP 5 , and indicated that siRNA knockdown of IPMK and IP3KB inhibited the ability of Wnt3a to stimulate the canonical ␤-catenin/lymphoid enhancer factor/T cell factor pathway. Is there evidence that other signaling processes depend on a putative IPK-dependent IP code?…”

Section: G Protein Activation Along With Expression Of the Four Evolmentioning

confidence: 99%

Alterations in an inositol phosphate code through synergistic activation of a G protein and inositol phosphate kinases

Otto

Kelly

Chiou

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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In mammals, many cellular stimuli evoke a response through G protein activation of phospholipase C, which results in the lipidderived production of inositol 1,4,5-trisphosphate (IP3). Although it is well established that IP3 is converted to numerous inositol phosphates (IPs) and pyrophosphates (PP-IPs) through the action of up to six classes of inositol phosphate kinases (IPKs), it is not clear that these metabolites are influenced by G protein signaling. Here we report that activation of G␣q leads to robust stimulation of IP3 to IP8 metabolism. To expose flux through these pathways, genetic perturbation was used to alter IP homeostasis. Coupled expression of a constitutively active G␣qQL and one or more IPK gene products synergistically generated dramatic changes in the patterns of intracellular IP messengers. Many distinct IP profiles were observed through the expression of different combinations of IPKs, including changes in previously unappreciated pools of IP 5 and IP6, two molecules widely viewed as stable metabolites. Our data link the activation of a trimeric G protein to a plethora of metabolites downstream of IP3 and provide a framework for suggesting that cells possess the machinery to produce an IPK-dependent IP code. We imply, but do not prove, that agonist-induced alterations in such a code would theoretically be capable of enhancing signaling complexity and specificity. The essential roles for IPKs in organism development and cellular adaptation are consistent with our hypothesis that such an IP code may be relevant to signaling pathways.Gq ͉ metabolomics ͉ phospholipase C ͉ signal transduction ͉ G protein-coupled receptor I n mammals, hundreds of G protein-coupled receptors (GPCR) and receptor tyrosine kinases (RTKs) are present and link to numerous intracellular signaling modules that, in combination, enable selective cellular responses. One of the most commonly activated signaling modules is the generation of the second messengers inositol 1,4,5-trisphosphate (IP 3 ) and 1,2-diacylglycerol by the action of phospholipase C isozymes (PLCs) on phosphatidylinositol 4,5-bisphosphate (PIP 2 ) (1-5). The ubiquity of PLC activation in response to a wide range of stimuli supports its central role in signaling, but also emphasizes that the production of two messengers alone, IP 3 and diacylglycerol, is insufficient to encode the breadth of specific cellular responses necessary for survival and adaptation. Therefore, it has been postulated that further signaling diversity could theoretically arise from the conversion of IP 3 to numerous inositol tetrakisphosphate (IP 4 ), inositol pentakisphosphate (IP 5 ), inositol hexakisphosphate (IP 6 ), and inositol pyrophosphate (PP-IP) molecules (2, 6-9). The production of these regulators occurs through the action of up to six classes of evolutionarily conserved IP kinase (IPK) gene products that include: IPMK/IPK2 (10-14), IPK1 (15-17), , ITPK/IP56K (21, 22), IP6K/ IHPK (23-25), and VIP1 (25-27) (Fig. 1). Genetic and biochemical studies of IPKs have provided v...

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Inositol Pentakisphosphate Mediates Wnt/β-Catenin Signaling

Cited by 48 publications

References 61 publications

p38 mitogen-activated protein kinase regulates canonical Wnt–β-catenin signaling by inactivation of GSK3β

p38 mitogen-activated protein kinase regulates canonical Wnt–β-catenin signaling by inactivation of GSK3β

High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance of Intact Zebrafish Embryos Detects Metabolic Changes Following Exposure to Teratogenic Polymethoxyalkenes from Algae

Alterations in an inositol phosphate code through synergistic activation of a G protein and inositol phosphate kinases

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