GO:0052866 phosphatidylinositol phosphate phosphatase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0052866 phosphatidylinositol phosphate phosphatase activity describes enzymes that remove a phosphate group from phosphatidylinositol phosphate lipids, a key reaction in phosphoinositide signaling.
• The reaction catalyzed is phosphatidylinositol phosphate(n) + H2O = phosphatidylinositol phosphate(n-1) + phosphate, as defined by QuickGO.
• PTEN is a well-known phosphatidylinositol phosphate phosphatase that acts on PI(3,4,5)P3, and its mutations are linked to cancer and autism-related syndromes.
• Myotubularin (MTM1) is a phosphatidylinositol phosphate phosphatase whose loss causes X-linked myotubular myopathy, highlighting the importance of this activity in muscle biology [2,8].
• Voltage-sensing phosphatases (VSPs) exhibit phosphatidylinositol phosphate phosphatase activity toward PI(3,4)P2, linking membrane voltage to phosphoinositide metabolism.
• Dysregulation of phosphatidylinositol phosphate phosphatases contributes to diverse diseases including cancer, neurodevelopmental disorders, and skeletal muscle disease [1,2,3,7].
Description
Phosphatidylinositol phosphate phosphatase activity (GO:0052866) is a molecular function that catalyzes the removal of a phosphate group from phosphatidylinositol phosphate lipids. This activity is central to phosphoinositide signaling, where the reversible phosphorylation of phosphatidylinositol species generates lipid second messengers that control cell growth, survival, membrane trafficking, and differentiation [1,4]. The QuickGO definition states: Catalysis of the reaction: phosphatidylinositol phosphate(n) + H2O = phosphatidylinositol phosphate(n-1) + phosphate. This reaction is the removal of a phosphate group from a phosphatidylinositol phosphate. Researchers study this activity because it directly opposes the action of phosphatidylinositol kinases and is essential for terminating or modulating lipid-based signals [1,8]. For example, the tumor suppressor PTEN is a phosphatidylinositol phosphate phosphatase that dephosphorylates PI(3,4,5)P3 to PI(4,5)P2, thereby antagonizing the PI3K/AKT pathway. Similarly, myotubularin (MTM1) dephosphorylates PI(3)P and PI(3,5)P2, and its deficiency leads to X-linked myotubular myopathy [2,8]. The importance of this activity extends to neurodevelopmental disorders, as mutations in phosphatidylinositol kinases and phosphatases can disrupt phosphoinositide signaling. Given its broad impact, GO:0052866 is a focus for understanding disease mechanisms and for developing targeted therapies.
phosphatidylinositol phosphate phosphatase activity At A Glance
| GO ID | GO:0052866 |
|---|---|
| GO term | phosphatidylinositol phosphate phosphatase activity |
| Ontology | molecular_function |
| Synonym | phosphoinositide phosphatase activity |
| Major function | Removal of a phosphate group from phosphatidylinositol phosphate lipids |
| Reaction | phosphatidylinositol phosphate(n) + H2O = phosphatidylinositol phosphate(n-1) + phosphate |
| Substrates | Phosphatidylinositol phosphates (e.g., PI(3,4,5)P3, PI(3)P, PI(3,4)P2) |
| Representative enzymes | PTEN, myotubularin (MTM1), voltage-sensing phosphatases (VSPs) |
| Disease relevance | Cancer, X-linked myotubular myopathy, neurodevelopmental syndromes, skeletal muscle disease |
What Is GO:0052866?
Phosphatidylinositol phosphate phosphatase activity (GO:0052866) is defined as the catalysis of the reaction: phosphatidylinositol phosphate(n) + H2O = phosphatidylinositol phosphate(n-1) + phosphate. In other words, it is the enzymatic removal of a phosphate group from a phosphatidylinositol phosphate molecule, converting it to a less phosphorylated form. This activity is synonymous with phosphoinositide phosphatase activity. It is a molecular function that acts on lipid substrates and is distinct from protein phosphatases. The reaction is hydrolytic, using water to cleave the phosphate ester bond, releasing inorganic phosphate. This definition is based on the QuickGO entry for GO:0052866.
Why Is phosphatidylinositol phosphate phosphatase activity Important in Cell Biology?
Phosphatidylinositol phosphate phosphatase activity is critically important because it directly regulates the levels of phosphoinositide second messengers that control fundamental cellular processes such as proliferation, survival, membrane trafficking, and autophagy [1,3,4]. By removing phosphate groups from phosphatidylinositol phosphates, these enzymes counteract kinases and ensure proper signal termination. Dysregulation of this activity is implicated in a wide range of human diseases, including cancer, where PTEN mutations are common, X-linked myotubular myopathy caused by MTM1 loss [2,8], and neurodevelopmental disorders linked to altered phosphoinositide signaling. Understanding this activity provides insights into disease mechanisms and potential therapeutic targets.
• PTEN, a phosphatidylinositol phosphate phosphatase, is one of the most frequently mutated tumor suppressors in human cancers.
• Loss of myotubularin (MTM1) phosphatase activity is the main cause of X-linked myotubular myopathy, a severe congenital muscle disorder.
• Defective lysosome reformation during autophagy, involving phosphoinositide phosphatases, causes skeletal muscle disease.
• Voltage-sensing phosphatases (VSPs) couple membrane voltage to phosphatidylinositol phosphate phosphatase activity, influencing excitability and signaling.
• Altered phosphoinositide signaling due to mutations in phosphatidylinositol kinases and phosphatases underlies neurodevelopmental syndromes.
• Phosphatidylinositol phosphate phosphatases are essential for autophagy and lysosomal function, impacting cellular homeostasis.
• They play roles in adrenal lipoma formation via PI(3,4,5)P3/AKT-dependent transdifferentiation.
• Studying these enzymes helps identify therapeutic targets for cancer, muscle disorders, and neurological conditions [1,2,7].
What Happens During phosphatidylinositol phosphate phosphatase activity?
Substrate recognition and binding
In simple terms: The enzyme finds and grabs a specific lipid molecule in the membrane.
Phosphatidylinositol phosphate phosphatases specifically recognize phosphatidylinositol phosphate substrates embedded in cellular membranes. For example, PTEN binds PI(3,4,5)P3 with high specificity, positioning its active site for catalysis. Myotubularin (MTM1) acts on PI(3)P and PI(3,5)P2, and its substrate specificity is determined by structural features of the phosphatase domain. The enzyme-substrate interaction often involves electrostatic interactions with the negatively charged lipid headgroup and hydrophobic insertion into the membrane.
Catalytic hydrolysis of the phosphate group
In simple terms: The enzyme uses water to cut off a phosphate group from the lipid.
The catalytic mechanism involves a nucleophilic attack by water on the phosphate ester bond, resulting in the removal of the phosphate group and release of inorganic phosphate. This reaction converts a phosphatidylinositol phosphate with n phosphates to one with n-1 phosphates. For instance, PTEN dephosphorylates PI(3,4,5)P3 to PI(4,5)P2, while VSPs dephosphorylate PI(3,4)P2 to PI(3)P. The reaction is dependent on the presence of a conserved cysteine residue in the CX5R motif within the phosphatase domain, which forms a covalent intermediate in some cases, though the exact mechanism varies among enzymes.
Product release and signal termination
In simple terms: After removing the phosphate, the enzyme releases the modified lipid, which stops a cellular signal.
Following catalysis, the product phosphatidylinositol phosphate is released from the active site, and the enzyme is ready for another cycle. This step is crucial for terminating lipid-based signals. For example, PTEN-mediated conversion of PI(3,4,5)P3 to PI(4,5)P2 reduces AKT activation, thereby suppressing cell survival and proliferation signals. In autophagy, phosphatidylinositol phosphate phosphatases such as myotubularin-related proteins are required for lysosome reformation, and their activity ensures proper turnover of autophagic membranes. Defects in product release or enzyme turnover can lead to accumulation of specific phosphoinositides and disease.
Regulation by protein-protein interactions and post-translational modifications
In simple terms: Other proteins and chemical tags can turn the enzyme on or off.
Phosphatidylinositol phosphate phosphatases are regulated by interacting partners and post-translational modifications. For example, PTEN activity is modulated by phosphorylation of its C-terminal tail, which affects its membrane recruitment and stability. Myotubularin is regulated by its interaction with MTMR2 and other proteins, and mutations that disrupt these interactions impair phosphatase activity. Voltage-sensing phosphatases are regulated by membrane voltage, coupling electrical signals to lipid metabolism. These regulatory mechanisms ensure that phosphatidylinositol phosphate phosphatase activity is tightly controlled in space and time.
Key Genes Involved in GO:0052866 phosphatidylinositol phosphate phosphatase activity
The following genes encode proteins with phosphatidylinositol phosphate phosphatase activity or are directly involved in its regulation, as supported by published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| PTEN | Dephosphorylates PI(3,4,5)P3 to PI(4,5)P2; tumor suppressor | Mutations linked to cancer and autism-related syndromes |
| MTM1 | Dephosphorylates PI(3)P and PI(3,5)P2; muscle maintenance | Loss causes X-linked myotubular myopathy [2,8] |
| MTMR2 | Phosphatidylinositol phosphate phosphatase; interacts with MTM1 | Implicated in Charcot-Marie-Tooth disease and muscle disease [3,8] |
| MTMR3 | Phosphatidylinositol phosphate phosphatase; regulates autophagy | Role in lysosome reformation and skeletal muscle disease |
| MTMR4 | Phosphatidylinositol phosphate phosphatase; regulates autophagy | Role in lysosome reformation and skeletal muscle disease |
| MTMR14 | Phosphatidylinositol phosphate phosphatase; muscle function | Linked to skeletal muscle disease and autophagy defects |
| VSP (e.g., Ci-VSP) | Voltage-sensing phosphatase; dephosphorylates PI(3,4)P2 | Couples membrane voltage to phosphoinositide signaling |
| PIP5KIγ | Phosphatidylinositol kinase (opposing activity) | Mutations cause neurodevelopmental syndrome with altered phosphoinositide signaling |
| FIG4 | Phosphatidylinositol 5-phosphatase; regulates PI(3,5)P2 | Associated with neurodegeneration and muscle disease |
| INPP4A | Phosphatidylinositol 4-phosphatase; acts on PI(3,4)P2 | Role in cancer and neurological disorders |
| INPP4B | Phosphatidylinositol 4-phosphatase; acts on PI(3,4)P2 | Tumor suppressor in some cancers |
| SAC1 | Phosphatidylinositol 4-phosphatase; regulates PI(4)P | Involved in Golgi function and disease |
| SYNJ1 | Phosphatidylinositol 5-phosphatase; synaptic function | Linked to Parkinson's disease and neurodegeneration |
| OCRL | Phosphatidylinositol 5-phosphatase; acts on PI(4,5)P2 | Mutations cause Lowe syndrome |
| INPP5E | Phosphatidylinositol 5-phosphatase; ciliary function | Mutations cause Joubert syndrome |
| PTEN-L | Long isoform of PTEN; secreted phosphatase | Modulates PI3K signaling in recipient cells |
How Is phosphatidylinositol phosphate phosphatase activity Regulated?
Phosphatidylinositol phosphate phosphatase activity is regulated at multiple levels. PTEN is controlled by phosphorylation, ubiquitination, and membrane recruitment, which affect its ability to dephosphorylate PI(3,4,5)P3. Myotubularin activity is regulated by its interaction with MTMR2 and other proteins, and mutations in the phosphatase domain abolish activity. Voltage-sensing phosphatases are directly regulated by membrane voltage, providing a rapid mechanism to couple electrical activity to lipid signaling. Additionally, the activity of these enzymes can be modulated by cellular localization and the availability of substrate lipids, which are themselves regulated by kinases and other phosphatases. In autophagy, phosphatidylinositol phosphate phosphatases are regulated by the autophagy machinery to ensure proper lysosome reformation.
phosphatidylinositol phosphate phosphatase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| PTEN | Cancer, autism-related syndromes | Knockout and point-mutation cell lines, xenograft models |
| MTM1 | X-linked myotubular myopathy | Knockout mice, patient-derived myotubes [2,8] |
| MTMR3/MTMR4/MTMR14 | Skeletal muscle disease, autophagy defects | Knockout cell lines, muscle-specific knockout mice |
| PIP5KIγ | Neurodevelopmental syndrome | Knock-in mice, patient iPSC-derived neurons |
| VSP | Neurological disorders (voltage-sensing) | Overexpression in cell lines, electrophysiology |
Cancer and PTEN mutations
PTEN is a phosphatidylinositol phosphate phosphatase that dephosphorylates PI(3,4,5)P3, thereby antagonizing the PI3K/AKT pathway. Mutations in PTEN that impair its phosphatase activity are associated with a wide range of cancers, including glioblastoma, breast, and prostate cancer. A comprehensive functional analysis of PTEN mutations revealed that many tumor-associated mutations reduce or abolish phosphatidylinositol phosphate phosphatase activity, and some mutations also contribute to autism-related syndromes. This highlights the critical role of this enzymatic activity in tumor suppression and normal development.
X-linked myotubular myopathy and muscle disease
Myotubularin (MTM1) is a phosphatidylinositol phosphate phosphatase that dephosphorylates PI(3)P and PI(3,5)P2. Lack of MTM1 phosphatase activity is the main cause of X-linked myotubular myopathy, a severe congenital muscle disorder characterized by hypotonia and respiratory failure [2,8]. Additionally, defective lysosome reformation during autophagy, which involves phosphatidylinositol phosphate phosphatases such as MTMR3, MTMR4, and MTMR14, causes skeletal muscle disease. These findings underscore the importance of this activity in muscle maintenance and autophagy.
Neurodevelopmental and neurological disorders
Altered phosphoinositide signaling due to mutations in phosphatidylinositol kinases and phosphatases can lead to neurodevelopmental syndromes. For example, de novo missense variants in PIP5KIγ, a phosphatidylinositol kinase, cause a neurodevelopmental syndrome associated with altered phosphoinositide signaling. While PIP5KIγ is a kinase, the balance between kinase and phosphatase activities is crucial, and mutations in phosphatases such as PTEN are also linked to autism-related syndromes. Furthermore, voltage-sensing phosphatases, which exhibit phosphatidylinositol phosphate phosphatase activity, may influence neuronal excitability and signaling.
Adrenal lipoma and metabolic transdifferentiation
Phosphatidylinositol phosphate phosphatase activity can influence adrenal lipoma formation via the PI(3,4,5)P3/AKT pathway. Studies have shown that transdifferentiation of adrenocortical cells into adipocytes is dependent on PI(3,4,5)P3/AKT signaling, which is normally kept in check by phosphatidylinositol phosphate phosphatases such as PTEN. This suggests that dysregulation of this activity may contribute to adrenal lipoma formation.
From phosphatidylinositol phosphate phosphatase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of PTEN phosphatase activity drive tumorigenesis? | PTEN knockout and point-mutation cell lines |
| How does MTM1 deficiency affect muscle structure and function? | MTM1 knockout mice and patient-derived myotubes [2,8] |
| What is the role of MTMR3/4/14 in autophagy and lysosome reformation? | Knockout cell lines and muscle-specific knockout mice |
| How do VSPs couple voltage to phosphoinositide signaling? | Overexpression of VSP in cell lines and electrophysiology |
| Do PIP5KIγ mutations alter phosphoinositide signaling in neurons? | Knock-in mice and patient iPSC-derived neurons |
| Can restoration of phosphatase activity rescue disease phenotypes? | Knock-in of wild-type phosphatase or overexpression [2,8] |
How to Study the phosphatidylinositol phosphate phosphatase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| In vitro phosphatase assay | Enzymatic removal of phosphate from phosphatidylinositol phosphates | Characterizing PTEN, MTM1, and VSP activity [1,4,8] |
| Mass spectrometry lipidomics | Relative levels of phosphoinositide species | Profiling changes in PI(3,4,5)P3, PI(3,4)P2, etc. [4,5] |
| CRISPR knockout | Loss of gene function | Studying PTEN, MTM1, MTMRs in disease models [1,2,3] |
| Point mutation knock-in | Effect of specific disease-associated mutations | Modeling PTEN mutations in cancer and autism |
| Overexpression | Gain of function | Assessing VSP or PTEN-L effects on signaling [1,4] |
| Fluorescent phosphoinositide probes | Real-time dynamics of specific lipids | Imaging PI(3,4,5)P3 or PI(4,5)P2 in live cells |
| Immunoblotting for downstream signaling | AKT phosphorylation and other readouts | Measuring pathway activation upon phosphatase loss [1,5] |
| Autophagy flux assays | Lysosome reformation and autophagic degradation | Evaluating MTMR roles in muscle disease |
Lipid phosphatase activity assays
Direct measurement of phosphatidylinositol phosphate phosphatase activity can be performed using in vitro assays with radiolabeled or fluorescently labeled phosphatidylinositol phosphate substrates. For example, PTEN activity is often measured using PI(3,4,5)P3 as a substrate and detecting released phosphate. Myotubularin activity can be assayed similarly with PI(3)P or PI(3,5)P2. These assays are essential for characterizing enzyme kinetics and the impact of disease-associated mutations.
Phosphoinositide profiling by mass spectrometry
Mass spectrometry-based lipidomics allows comprehensive profiling of phosphatidylinositol phosphate species in cells and tissues. This method can quantify changes in PI(3,4,5)P3, PI(3,4)P2, PI(4,5)P2, and other phosphoinositides upon modulation of phosphatase activity [4,5]. Such profiling is crucial for understanding how phosphatidylinositol phosphate phosphatases shape the cellular lipid landscape in health and disease.
Genetic and pharmacological perturbation
CRISPR/Cas9-mediated knockout, point mutations, and overexpression are powerful approaches to study the function of phosphatidylinositol phosphate phosphatases. For instance, knockout of PTEN in cell lines leads to accumulation of PI(3,4,5)P3 and activation of AKT. Knockout of MTM1 in muscle cells recapitulates features of myotubular myopathy. These models enable researchers to dissect the specific contributions of phosphatase activity to cellular phenotypes.
Imaging of phosphoinositide dynamics
Genetically encoded fluorescent probes that bind specific phosphoinositides can be used to visualize the dynamics of phosphatidylinositol phosphates in live cells. For example, the PH domain of AKT fused to GFP reports PI(3,4,5)P3 levels, and its changes upon phosphatase activity can be monitored. Such imaging approaches provide spatiotemporal insights into how phosphatidylinositol phosphate phosphatases regulate signaling at the membrane.
How CRISPR Can Be Used to Study GO:0052866 phosphatidylinositol phosphate phosphatase activity
Knockout
CRISPR/Cas9-mediated knockout is widely used to study the loss of phosphatidylinositol phosphate phosphatase function. For example, PTEN knockout cell lines exhibit elevated PI(3,4,5)P3 and increased AKT phosphorylation, mimicking cancer-associated phenotypes. MTM1 knockout in muscle cells or mice recapitulates key features of X-linked myotubular myopathy [2,8]. Knockout of MTMR3, MTMR4, or MTMR14 impairs autophagy and lysosome reformation, leading to skeletal muscle defects. These models are essential for understanding the physiological roles of these enzymes.
Point Mutation
Point mutations identified in patients can be introduced using CRISPR/Cas9 to model disease-associated variants. For instance, a comprehensive functional analysis of PTEN mutations using point-mutation knock-in revealed that many tumor- and autism-associated mutations impair phosphatidylinositol phosphate phosphatase activity. Similarly, mutations in MTM1 that abolish phosphatase activity cause myotubular myopathy [2,8]. Such models allow researchers to dissect the specific effects of individual mutations on enzyme function and downstream signaling.
Knock-in
Knock-in of wild-type or tagged versions of phosphatidylinositol phosphate phosphatases can be used to study protein localization, interactions, and function. For example, knock-in of fluorescently tagged PTEN allows real-time imaging of its membrane recruitment and activity. Knock-in of MTM1 with a tag can help identify interacting partners and substrates in muscle cells. These models are valuable for understanding the spatiotemporal regulation of phosphatase activity.
Overexpression
Overexpression of phosphatidylinositol phosphate phosphatases is used to assess gain-of-function effects. For example, overexpression of PTEN or its long isoform PTEN-L reduces PI(3,4,5)P3 levels and inhibits AKT signaling, leading to decreased cell proliferation. Overexpression of voltage-sensing phosphatases in cell lines has been used to study their voltage-dependent phosphatase activity toward PI(3,4)P2. Overexpression models complement loss-of-function studies and help establish causality.
How EDITGENE Supports phosphatidylinositol phosphate phosphatase activity Research
Researchers studying phosphatidylinositol phosphate phosphatase activity-related genes often need to determine whether a candidate gene is causally involved in a specific cellular process or disease. This requires precise genetic models that can knockout, mutate, or overexpress the gene of interest in relevant cell types. EDITGENE provides a comprehensive suite of CRISPR-based services to accelerate such research.
Contact EDITGENE today to design your custom CRISPR model for phosphatidylinositol phosphate phosphatase activity research.
Frequently Asked Questions About phosphatidylinositol phosphate phosphatase activity
What is phosphatidylinositol phosphate phosphatase activity?
It is a molecular function (GO:0052866) that catalyzes the removal of a phosphate group from phosphatidylinositol phosphate lipids, as defined by the reaction phosphatidylinositol phosphate(n) + H2O = phosphatidylinositol phosphate(n-1) + phosphate.
What genes are involved in phosphatidylinositol phosphate phosphatase activity?
Key genes include PTEN, MTM1, MTMR2, MTMR3, MTMR4, MTMR14, VSP, FIG4, INPP4A, INPP4B, SAC1, SYNJ1, OCRL, and INPP5E [1,2,3,4,5,6,7,8].
How is phosphatidylinositol phosphate phosphatase activity linked to cancer?
PTEN is a phosphatidylinositol phosphate phosphatase that dephosphorylates PI(3,4,5)P3 to PI(4,5)P2, antagonizing the PI3K/AKT pathway. Mutations that impair its activity are common in many cancers.
What diseases are caused by mutations in phosphatidylinositol phosphate phosphatases?
Diseases include X-linked myotubular myopathy (MTM1), cancer and autism-related syndromes (PTEN), skeletal muscle disease (MTMRs), and neurodevelopmental syndromes (PIP5KIγ) [1,2,3,7].
How can I study phosphatidylinositol phosphate phosphatase activity in the lab?
Common methods include in vitro phosphatase assays, mass spectrometry lipidomics, CRISPR knockout or point-mutation knock-in, overexpression, and fluorescent phosphoinositide probes [1,4,5,8].
What is the role of myotubularin in muscle disease?
Myotubularin (MTM1) dephosphorylates PI(3)P and PI(3,5)P2, and lack of its phosphatase activity is the main cause of X-linked myotubular myopathy [2,8].
How does voltage-sensing phosphatase relate to phosphatidylinositol phosphate phosphatase activity?
Voltage-sensing phosphatases (VSPs) exhibit phosphatidylinositol phosphate phosphatase activity toward PI(3,4)P2, coupling membrane voltage to phosphoinositide signaling.
What is the difference between phosphatidylinositol phosphate phosphatase and protein phosphatase?
Phosphatidylinositol phosphate phosphatases act on lipid substrates (phosphatidylinositol phosphates), while protein phosphatases remove phosphate from proteins.
Can CRISPR be used to model phosphatidylinositol phosphate phosphatase mutations?
Yes, CRISPR/Cas9 can introduce knockout, point mutations, or knock-ins to model disease-associated mutations in genes like PTEN and MTM1 [1,2].
What are the substrates of phosphatidylinositol phosphate phosphatases?
Substrates include PI(3,4,5)P3, PI(3)P, PI(3,5)P2, PI(3,4)P2, PI(4,5)P2, and other phosphatidylinositol phosphates, depending on the enzyme [1,4,6,8].
Conclusion
Phosphatidylinositol phosphate phosphatase activity (GO:0052866) is a fundamental enzymatic function that regulates phosphoinositide signaling by removing phosphate groups from phosphatidylinositol phosphate lipids. Its importance is underscored by the diverse diseases linked to its dysregulation, including cancer, X-linked myotubular myopathy, and neurodevelopmental disorders [1,2,7]. Studying this activity requires robust experimental models, and CRISPR-based approaches offer precise tools to dissect gene function. EDITGENE provides comprehensive services to support such research, from knockout and knock-in models to library screening and bioinformatics.
References
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- 2. Moschovaki-Filippidou F et al.. 2025. Lack of myotubularin phosphatase activity is the main cause of X-linked myotubular myopathy.. JCI Insight 10(22) PMID: 41086017
- 3. McGrath MJ et al.. 2021. Defective lysosome reformation during autophagy causes skeletal muscle disease.. J Clin Invest 131(1) PMID: 33119550
- 4. Kurokawa T et al.. 2012. 3' Phosphatase activity toward phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] by voltage-sensing phosphatase (VSP).. Proc Natl Acad Sci U S A 109(25):10089-94 PMID: 22645351
- 5. Yanai S et al.. 2025. Adrenal lipoma formation via PI(3,4,5)P(3)/AKT-dependent transdifferentiation of adrenocortical cells into adipocytes.. Proc Natl Acad Sci U S A 122(37):e2510306122 PMID: 40924445
- 6. Mack SE et al.. 1984. Evidence for a specific phosphatidylinositol 4-phosphate phosphatase in human erythrocyte membranes.. J Lipid Res 25(1):75-85 PMID: 6323606
- 7. Morleo M et al.. 2023. De novo missense variants in phosphatidylinositol kinase PIP5KIγ underlie a neurodevelopmental syndrome associated with altered phosphoinositide signaling.. Am J Hum Genet 110(8):1377-1393 PMID: 37451268
- 8. Blondeau F et al.. 2000. Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway.. Hum Mol Genet 9(15):2223-9 PMID: 11001925
