ArticleProceedings of the National Academy of Sciences of the United States of America2010
Inositol hexakisphosphate kinase-2 acts as an effector of the vertebrate Hedgehog pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Functions, Mechanisms, and therapeutic applications of the inositol pyrophosphates 5PP-InsPJournal of cardiovascular translational research · 2024Review
- Article
- Identifying prognostic characteristics of m6A-related glycolysis gene and predicting the immune infiltration landscape in bladder cancer.Cancer cell international · 2023Article
- The BMP signaling gradient is interpreted through concentration thresholds in dorsal-ventral axial patterning.PLoS biology · 2021Article
- The Key Role of IPMolecules (Basel, Switzerland) · 2020Review
- Targeting the Inositol Pyrophosphate Biosynthetic Enzymes in Metabolic Diseases.Molecules (Basel, Switzerland) · 2020Review
- The role of A-kinase anchoring proteins in cardiac oxidative stress.Biochemical Society transactions · 2019Review
- Fungal Kinases With a Sweet Tooth: Pleiotropic Roles of Their Phosphorylated Inositol Sugar Products in the Pathogenicity ofFrontiers in cellular and infection microbiology · 2019Review
- The inositol pyrophosphate pathway in health and diseases.Biological reviews of the Cambridge Philosophical Society · 2018Review
- The significance of the 1-kinase/1-phosphatase activities of the PPIP5K family.Advances in biological regulation · 2017Review
- Adipocyte-specific deletion of Ip6k1 reduces diet-induced obesity by enhancing AMPK-mediated thermogenesis.The Journal of clinical investigation · 2016Article
- TNP [N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine] ameliorates diet induced obesity and insulin resistance via inhibition of the IP6K1 pathway.Molecular metabolism · 2016Article
- Towards pharmacological intervention in inositol pyrophosphate signalling.Biochemical Society transactions · 2016Review
- Inositol hexakisphosphate kinase-1 regulates behavioral responses via GSK3 signaling pathways.Molecular psychiatry · 2014Article
- The enzymes of human diphosphoinositol polyphosphate metabolism.The FEBS journal · 2014Review
- Evidence of a role of inositol polyphosphate 5-phosphatase INPP5E in cilia formation in zebrafish.Vision research · 2012Article
- Defining signal transduction by inositol phosphates.Sub-cellular biochemistry · 2012Review
- Inositol pyrophosphates as mammalian cell signals.Science signaling · 2011Review
- Casein kinase-2 mediates cell survival through phosphorylation and degradation of inositol hexakisphosphate kinase-2.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
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Authors and funding
2 authors at 1 institution in 1 country.
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Abstract
Inositol phosphate (IP) kinases constitute an emerging class of cellular kinases linked to multiple cellular activities. Here, we report a previously uncharacterized cellular function in Hedgehog (Hh) signaling for the IP kinase designated inositol hexakisphosphate kinase-2 (IP6K2) that produces diphosphoryl inositol phosphates (PP-IPs). In zebrafish embryos, IP6K2 activity was required for normal development of craniofacial structures, somites, and neural crest cells. ip6k2 depletion in both zebrafish and mammalian cells also inhibited Hh target gene expression. Inhibiting IP(6) kinase activity using N(2)-(m-(trifluoromethy)lbenzyl) N(6)-(p-nitrobenzyl)purine (TNP) resulted in altered Hh signal transduction. In zebrafish, restoring IP6K2 levels with exogenous ip6k2 mRNA reversed the effects of IP6K2 depletion. Furthermore, overexpression of ip6k2 in mammalian cells enhanced the Hh pathway response, suggesting IP6K2 is a positive regulator of Hh signaling. Perturbations from IP6K2 depletion or TNP were reversed by overexpressing smoM2, gli1, or ip6k2. Moreover, the inhibitory effect of cyclopamine was reversed by overexpressing ip6k2. This identified roles for the inositol kinase pathway in early vertebrate development and tissue morphogenesis, and in Hh signaling. We propose that IP6K2 activity is required at the level or downstream of Smoothened but upstream of the transcription activator Gli1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.