GO:0034597 phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0034597 describes the enzymatic removal of the 4-phosphate from phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2), yielding phosphatidylinositol-3-phosphate and inorganic phosphate.
• This activity is distinct from the more widely studied 5-phosphatases and 3-phosphatases, and it contributes to the complex regulation of phosphoinositide signaling.
• The INPP4 family enzymes, particularly INPP4A and INPP4B, are the principal proteins associated with this activity in human cells.
• INPP4B can also dephosphorylate PtdIns(3,4,5)P3 at the 4-position, acting as a tumor suppressor in some contexts, which has earned it the description of a 'PTEN-like' enzyme.
• Dysregulation of this activity has been linked to cancer, neurological disorders, and defects in membrane trafficking and receptor endocytosis.
• CRISPR-based knockout, point-mutation, and knock-in models are essential tools for dissecting the precise roles of this enzymatic activity in health and disease.
Description
Phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity (GO:0034597) is a molecular function that catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) to phosphatidylinositol-3-phosphate and phosphate. This reaction is part of the broader network of phosphoinositide phosphatases that counterbalance the actions of lipid kinases, thereby shaping the spatial and temporal dynamics of signaling lipids. The activity is attributed to members of the inositol polyphosphate 4-phosphatase family, notably INPP4A and INPP4B, which remove the 4-phosphate from specific phosphoinositides. Understanding this activity is critical because PtdIns(4,5)P2 is a central signaling molecule that regulates membrane trafficking, ion channels, and cytoskeletal dynamics, and its conversion to PtdIns(3)P has distinct downstream consequences. Despite its importance, the 4-phosphatase activity has historically been overshadowed by the more extensively characterized 5-phosphatases (e.g., OCRL, INPP5B) and 3-phosphatase PTEN. However, emerging evidence indicates that INPP4B, a member of this family, can also dephosphorylate PtdIns(3,4,5)P3 at the 4-position, thereby directly opposing PI3K signaling and acting as a tumor suppressor in certain tissues. This dual specificity has sparked renewed interest in the 4-phosphatase family as potential therapeutic targets and biomarkers in cancer. Furthermore, the activity has been implicated in neuronal function and viral infection responses, underscoring its broad physiological relevance. For researchers, GO:0034597 provides a precise annotation for experiments aimed at measuring lipid phosphatase activity, identifying new enzymes, or dissecting signaling pathways. The availability of CRISPR-engineered cell models now allows rigorous testing of the causal roles of these enzymes in cellular processes and disease models.
phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity At A Glance
| GO ID | GO:0034597 |
|---|---|
| GO term | phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity |
| Ontology | molecular_function |
| Synonym | 1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate 4-phosphohydrolase activity; phosphatidyl-myo-inositol-4,5-bisphosphate 4-phosphohydrolase activity |
| Major function | Catalyzes the removal of the 4-phosphate from PtdIns(4,5)P2 to generate PtdIns(3)P and phosphate. |
| Major enzymes | INPP4A, INPP4B (inositol polyphosphate 4-phosphatases). |
| Substrate | 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate (PtdIns(4,5)P2). |
| Product | 1-phosphatidyl-1D-myo-inositol 3-phosphate (PtdIns(3)P) and phosphate. |
| Cofactors | Requires Mg2+ or Mn2+ for activity (typical for phosphoinositide phosphatases). |
| Disease links | Cancer (tumor suppressor role of INPP4B), neurological disorders, viral infection. |
What Is GO:0034597?
Phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity (GO:0034597) is defined as the catalysis of the reaction: 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1-phosphatidyl-1D-myo-inositol 3-phosphate + phosphate. In simpler terms, it is an enzyme activity that removes the phosphate group at the 4-position of the inositol ring from PtdIns(4,5)P2, producing PtdIns(3)P and free phosphate. This activity is distinct from 5-phosphatases and 3-phosphatases, which remove phosphates from different positions.
Why Is phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity Important in Cell Biology?
Phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity is important because it directly modulates the levels of two critical signaling lipids: PtdIns(4,5)P2 and PtdIns(3)P. PtdIns(4,5)P2 is a precursor for second messengers like IP3 and DAG, and it regulates membrane trafficking, endocytosis, and ion channel activity. By converting PtdIns(4,5)P2 to PtdIns(3)P, this activity can terminate PtdIns(4,5)P2-dependent signals and simultaneously generate PtdIns(3)P, which is key for endosomal sorting and autophagy. Moreover, the ability of INPP4B to dephosphorylate PtdIns(3,4,5)P3 links this activity directly to the PI3K/AKT pathway, a central node in cancer. Thus, understanding GO:0034597 is essential for deciphering how cells balance phosphoinositide signals in health and disease.
• Regulates the availability of PtdIns(4,5)P2, a master regulator of membrane dynamics and signaling.
• Generates PtdIns(3)P, which is essential for endosomal trafficking and autophagy.
• INPP4B acts as a tumor suppressor by dephosphorylating PtdIns(3,4,5)P3, opposing PI3K/AKT signaling.
• Loss of INPP4B is associated with poor prognosis in breast, prostate, and ovarian cancers.
• The activity is implicated in neuronal function and may be altered in neurodegenerative conditions.
• Plays a role in host response to viral infection, as suggested by transcriptomic studies of TBEV-infected cells.
• Provides a potential therapeutic target for cancers with hyperactive PI3K signaling.
• Enables precise experimental dissection of phosphoinositide signaling using CRISPR knockout models.
• Contributes to the regulation of GPCR endocytosis through modulation of PtdIns(4,5)P2 synthesis.
• Represents a distinct branch of PI3K signaling that is less studied than PTEN, offering new research opportunities.
Molecular Mechanism of phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity
Substrate recognition and binding
In simple terms: The enzyme grabs the lipid substrate PtdIns(4,5)P2 in the membrane.
The 4-phosphatase enzymes, such as INPP4A and INPP4B, specifically recognize phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) as a substrate. This recognition involves a conserved catalytic domain that binds the inositol headgroup and the 4-phosphate. The enzymes are recruited to membranes where PtdIns(4,5)P2 is enriched, often through electrostatic interactions with negatively charged lipids or via protein-protein interactions.
Catalytic hydrolysis of the 4-phosphate
In simple terms: The enzyme cuts off the phosphate at the 4-position using water.
Once bound, the enzyme catalyzes the hydrolysis of the phosphoester bond at the 4-position of the inositol ring, releasing inorganic phosphate and producing phosphatidylinositol-3-phosphate (PtdIns(3)P). This reaction requires a divalent metal ion, typically Mg2+ or Mn2+, which stabilizes the leaving group and activates a water molecule for nucleophilic attack. The catalytic mechanism is similar to other phosphoinositide phosphatases, involving a conserved cysteine or histidine residue in the active site.
Product release and membrane dissociation
In simple terms: After the reaction, the products leave the enzyme and the enzyme can act again.
Following catalysis, the products PtdIns(3)P and phosphate are released from the active site. PtdIns(3)P may remain in the membrane and recruit effector proteins containing FYVE or PX domains, thereby propagating downstream signals. The enzyme may then dissociate from the membrane or remain associated to catalyze additional rounds of substrate turnover, depending on its regulatory interactions.
Regulation by protein-protein interactions and post-translational modifications
In simple terms: Other proteins and chemical tags can turn the enzyme on or off.
The activity of 4-phosphatases is regulated by various mechanisms. For example, INPP4B can be phosphorylated, which may affect its localization or catalytic activity. Additionally, interaction with scaffold proteins or membrane-targeting subunits can modulate substrate access. The enzyme's activity is also influenced by the local lipid environment and the availability of PtdIns(4,5)P2, which is dynamically controlled by kinases and other phosphatases.
Distinction from other phosphoinositide phosphatases
In simple terms: This enzyme is different from other similar enzymes because it removes a specific phosphate.
The 4-phosphatase activity is distinct from 5-phosphatases (e.g., OCRL, INPP5B) and 3-phosphatases (e.g., PTEN). While 5-phosphatases remove the 5-phosphate from PtdIns(4,5)P2 to generate PtdIns(4)P, and PTEN removes the 3-phosphate from PtdIns(3,4,5)P3 to generate PtdIns(4,5)P2, the 4-phosphatase removes the 4-phosphate from PtdIns(4,5)P2 to produce PtdIns(3)P. This unique positional specificity allows for precise control of phosphoinositide pools and downstream signaling.
Key Genes Involved in GO:0034597 phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity
The following genes encode proteins that exhibit or are directly associated with phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity, along with related regulatory proteins.
| Gene | Major Role | Research Relevance |
|---|---|---|
| INPP4A | Inositol polyphosphate 4-phosphatase type I; hydrolyzes PtdIns(4,5)P2 and PtdIns(3,4)P2 | Implicated in neuronal function and tumor suppression; knockout models show neurological defects. |
| INPP4B | Inositol polyphosphate 4-phosphatase type II; hydrolyzes PtdIns(3,4)P2 and PtdIns(3,4,5)P3 | Tumor suppressor in breast, prostate, ovarian cancers; key regulator of PI3K/AKT pathway. |
| PTEN | 3-phosphatase that dephosphorylates PtdIns(3,4,5)P3 | Frequently mutated in cancers; functional counterpart to INPP4B in PI3K signaling. |
| PIK3CA | Catalytic subunit of PI3K; synthesizes PtdIns(3,4,5)P3 | Oncogene; provides substrate for INPP4B; mutations drive cancer. |
| PIK3CB | PI3K catalytic subunit beta | Involved in GPCR signaling and endocytosis; modulates PtdIns(4,5)P2 synthesis. |
| PIK3CD | PI3K catalytic subunit delta | Immune cell signaling; potential crosstalk with 4-phosphatases. |
| PIK3R1 | Regulatory subunit of PI3K | Mutations affect PI3K activity and downstream phosphoinositide levels. |
| ARRB1 | Beta-arrestin 1; scaffolds PI4K and PIP5K to promote PtdIns(4,5)P2 synthesis | Regulates GPCR endocytosis; may influence substrate availability for 4-phosphatases. |
| ARRB2 | Beta-arrestin 2; similar to ARRB1 | Modulates PtdIns(4,5)P2 synthesis during endocytosis. |
| PIP5K1A | Phosphatidylinositol-4-phosphate 5-kinase type 1 alpha | Generates PtdIns(4,5)P2, the substrate for 4-phosphatases. |
| PIP5K1B | Phosphatidylinositol-4-phosphate 5-kinase type 1 beta | Alternative PtdIns(4,5)P2 synthesizing enzyme. |
| PIP5K1C | Phosphatidylinositol-4-phosphate 5-kinase type 1 gamma | Important in neuronal and focal adhesion dynamics. |
| PI4KA | Phosphatidylinositol 4-kinase alpha | Produces PtdIns(4)P, precursor for PtdIns(4,5)P2. |
| PI4KB | Phosphatidylinositol 4-kinase beta | Involved in Golgi and viral replication; affects substrate supply. |
| OCRL | 5-phosphatase that converts PtdIns(4,5)P2 to PtdIns(4)P | Mutations cause Lowe syndrome; contrasts with 4-phosphatase activity. |
| INPP5B | 5-phosphatase; hydrolyzes PtdIns(4,5)P2 | Similar to OCRL; provides comparative tool for studying 4-phosphatase specificity. |
| SYNJ1 | Synaptojanin 1; 5-phosphatase | Regulates synaptic vesicle recycling; potential interplay with 4-phosphatases. |
| MTM1 | Myotubularin; 3-phosphatase | Mutations cause myotubular myopathy; distinct from 4-phosphatase. |
How Is phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity Regulated?
The activity of phosphatidylinositol-4,5-bisphosphate 4-phosphatase is regulated at multiple levels. First, substrate availability is controlled by the balance of PI4K and PIP5K kinases that synthesize PtdIns(4,5)P2, as well as by 5-phosphatases that consume it. Second, the enzymes themselves can be regulated by post-translational modifications; for instance, INPP4B is subject to phosphorylation and ubiquitination, which affect its stability and localization. Third, protein-protein interactions, such as binding to beta-arrestins during GPCR endocytosis, can recruit the enzymes to specific membrane compartments where their substrate is enriched. Finally, the activity can be influenced by the local lipid composition and the presence of divalent cations like Mg2+. These layers of regulation ensure that the 4-phosphatase activity is precisely tuned to cellular needs.
phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| INPP4B | Breast cancer, prostate cancer, ovarian cancer; tumor suppressor | Knockout in MCF-7 or PC-3 cells; xenograft mouse models |
| INPP4A | Neurodegeneration, synaptic dysfunction | Neuron-specific knockout mice; iPSC-derived neurons |
| PTEN | Cowden syndrome, multiple cancers | Knockout in cancer cell lines; comparison with INPP4B |
| PIK3CA | Breast cancer, colorectal cancer; oncogene | Point mutation knock-in (e.g., H1047R) in cell lines |
| ARRB1/2 | GPCR endocytosis, potential role in viral infection | Knockout in HEK293 cells; live-cell imaging |
Cancer
INPP4B, a key enzyme with 4-phosphatase activity, is frequently downregulated or lost in several cancers, including breast, prostate, and ovarian carcinomas. Its ability to dephosphorylate PtdIns(3,4,5)P3 at the 4-position directly antagonizes PI3K/AKT signaling, and loss of INPP4B leads to hyperactivation of AKT, promoting tumor growth and survival. This tumor suppressor function is reminiscent of PTEN, although the two enzymes act on different phosphoinositide substrates. Consequently, INPP4B status is being explored as a prognostic biomarker and a potential therapeutic target.
Neurological disorders
Phosphoinositide signaling is critical for neuronal function, and enzymes that regulate PtdIns(4,5)P2 levels are implicated in neurological disorders. INPP4A, which exhibits 4-phosphatase activity, is highly expressed in the brain, and its dysfunction has been linked to neurodegeneration and synaptic defects. Studies in model organisms suggest that loss of INPP4A leads to neuronal degeneration, possibly due to altered phosphoinositide homeostasis. Furthermore, transcriptomic profiling of TBEV-infected neurons and astrocytes revealed changes in genes related to phosphoinositide metabolism, suggesting a role in viral neuropathogenesis.
Infectious diseases
Emerging evidence points to a role for phosphoinositide 4-phosphatases in host-pathogen interactions. For example, infection with tick-borne encephalitis virus (TBEV) alters the expression of multiple genes involved in lipid signaling, including potential regulators of PtdIns(4,5)P2 metabolism. Given that many viruses hijack phosphoinositide pathways for replication and entry, the 4-phosphatase activity may influence viral propagation and could be a target for antiviral strategies.
From phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of INPP4B increase AKT signaling? | INPP4B knockout cell lines (e.g., MCF-7) generated by CRISPR |
| What is the effect of a specific point mutation in the catalytic domain of INPP4B? | Point mutation knock-in via CRISPR in cancer cell lines |
| How does INPP4B localization affect its function? | Knock-in of fluorescent tags (e.g., GFP) at the endogenous locus |
| Can overexpression of INPP4B suppress tumor growth? | Overexpression of INPP4B in cancer cell lines and xenografts |
| What is the role of INPP4A in neuronal survival? | Conditional knockout in mouse brain or iPSC-derived neurons |
| How does 4-phosphatase activity affect GPCR endocytosis? | Knockout of INPP4B in cells with tagged GPCRs; imaging |
How to Study the phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| In vitro phosphatase assay | Enzymatic activity and kinetics | Validation of INPP4A/B activity on PtdIns(4,5)P2 |
| CRISPR knockout screening | Gene essentiality and synthetic lethality | Identifying modifiers of INPP4B loss in cancer |
| Lipidomics (mass spectrometry) | Phosphoinositide species levels | Quantifying changes in PtdIns(4,5)P2 and PtdIns(3)P |
| Live-cell imaging with PH domains | Spatiotemporal dynamics of phosphoinositides | Studying GPCR endocytosis and membrane trafficking |
| Western blotting | Protein expression and phosphorylation | Assessing AKT activation upon INPP4B loss |
| Immunofluorescence | Subcellular localization of enzymes | Determining membrane recruitment of INPP4B |
| RNA-seq | Transcriptional changes | Profiling gene expression in knockout models |
| Co-immunoprecipitation | Protein-protein interactions | Identifying regulators of 4-phosphatases |
Lipid phosphatase activity assays
To directly measure phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity, researchers use in vitro assays with radiolabeled or fluorescently labeled PtdIns(4,5)P2 as substrate. The release of phosphate or the formation of PtdIns(3)P can be quantified by chromatography or mass spectrometry. These assays are essential for validating enzyme specificity and kinetics.
CRISPR-based genetic screens
Genome-wide CRISPR knockout screens can identify genes that modulate phosphoinositide signaling or that are synthetic lethal with INPP4B loss. Such screens have been used to uncover vulnerabilities in cancer cells lacking INPP4B. Libraries targeting lipid kinases and phosphatases are particularly useful for dissecting the 4-phosphatase pathway.
Phosphoinositide profiling by mass spectrometry
Mass spectrometry-based lipidomics allows comprehensive profiling of phosphoinositide species in cells with altered 4-phosphatase activity. This method can quantify changes in PtdIns(4,5)P2, PtdIns(3)P, and other lipids, providing a systems-level view of the pathway.
Live-cell imaging of phosphoinositide dynamics
Genetically encoded fluorescent probes (e.g., GFP-tagged PH domains) that specifically bind PtdIns(4,5)P2 or PtdIns(3)P enable real-time visualization of lipid dynamics in living cells. These probes can be used to study how 4-phosphatase activity affects membrane trafficking and receptor endocytosis.
How CRISPR Can Be Used to Study GO:0034597 phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity
Knockout
CRISPR-Cas9 knockout of INPP4A or INPP4B is a powerful approach to study the loss-of-function phenotypes of phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity. Knockout cell lines can be generated by introducing frameshift mutations in early exons, leading to complete loss of protein. These models have been used to demonstrate that INPP4B loss leads to hyperactivation of AKT and increased cell proliferation. Knockout mice for INPP4A exhibit neurological defects, highlighting the importance of this activity in the brain.
Point Mutation
Point mutations in the catalytic domain of INPP4B can be introduced using CRISPR-Cas9 homology-directed repair (HDR) to specifically ablate enzymatic activity without affecting protein stability or interactions. Such models are invaluable for distinguishing the catalytic-dependent functions of the enzyme from its scaffolding roles. For example, mutation of the conserved cysteine in the CX5R motif abolishes phosphatase activity and can be used to test whether tumor suppression requires catalytic activity.
Knock-in
Knock-in of epitope tags (e.g., FLAG, HA) or fluorescent proteins (e.g., GFP) at the endogenous INPP4B locus allows for real-time tracking of the enzyme's localization and interactions. This approach preserves endogenous regulation and can reveal dynamic changes in enzyme distribution upon stimulation. Knock-in of disease-associated mutations (e.g., those found in cancer) can also be used to model their functional consequences.
Overexpression
Overexpression of wild-type or mutant INPP4B in cell lines is a complementary approach to knockout studies. It can be achieved by lentiviral transduction or by CRISPR-mediated knock-in of a strong promoter. Overexpression of INPP4B has been shown to suppress tumor growth and reduce AKT phosphorylation, confirming its tumor suppressor function. This approach is useful for gain-of-function experiments and for testing the effects of specific mutations.
How EDITGENE Supports phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity Research
Researchers studying phosphatidylinositol-4,5-bisphosphate 4-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 manipulation, which can be achieved through CRISPR-based knockout, point mutation, knock-in, or overexpression models. EDITGENE provides a comprehensive suite of services to generate such models efficiently and reliably.
Contact EDITGENE today to design your custom CRISPR model for phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity research.
Frequently Asked Questions About phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity
What is phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity?
It is an enzymatic activity (GO:0034597) that removes the 4-phosphate from PtdIns(4,5)P2 to produce PtdIns(3)P and phosphate.
What genes are involved in phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity?
The main genes are INPP4A and INPP4B, which encode inositol polyphosphate 4-phosphatases.
Which diseases are associated with INPP4B mutations?
INPP4B loss is associated with breast, prostate, and ovarian cancers, where it acts as a tumor suppressor.
How is phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity measured?
It can be measured using in vitro phosphatase assays with radiolabeled PtdIns(4,5)P2, or by lipidomics to quantify product formation.
What is the difference between INPP4B and PTEN?
Both are tumor suppressors that oppose PI3K signaling, but PTEN removes the 3-phosphate from PtdIns(3,4,5)P3, while INPP4B removes the 4-phosphate from PtdIns(3,4)P2 and PtdIns(3,4,5)P3.
Can CRISPR be used to study phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity?
Yes, CRISPR knockout, point mutation, and knock-in models are widely used to dissect the function of INPP4A and INPP4B.
What are the substrates of phosphatidylinositol-4,5-bisphosphate 4-phosphatase?
The primary substrate is PtdIns(4,5)P2, but INPP4B can also act on PtdIns(3,4)P2 and PtdIns(3,4,5)P3.
Is phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity involved in neuronal function?
Yes, INPP4A is highly expressed in the brain and its loss leads to neurodegeneration in models.
How does phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity affect endocytosis?
By modulating PtdIns(4,5)P2 levels, it can influence GPCR endocytosis, as beta-arrestin-dependent PtdIns(4,5)P2 synthesis is required for this process.
What research methods are used to study phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity?
Common methods include in vitro phosphatase assays, lipidomics, live-cell imaging with PH domains, and CRISPR-based genetic screens.
Conclusion
Phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity (GO:0034597) is a critical enzymatic function that regulates phosphoinositide signaling by converting PtdIns(4,5)P2 to PtdIns(3)P. Its main effectors, INPP4A and INPP4B, play key roles in cancer suppression, neuronal function, and membrane trafficking. Despite its importance, this activity remains less studied than other phosphoinositide phosphatases, offering ample opportunities for discovery. Advances in CRISPR-based models and lipidomics now enable precise interrogation of this pathway in health and disease.
References
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- 3. Jung SR et al.. 2021. β-arrestin-dependent PI(4,5)P(2) synthesis boosts GPCR endocytosis.. Proc Natl Acad Sci U S A 118(17) PMID: 33879605
- 4. Hamila SA et al.. 2021. The INPP4B paradox: Like PTEN, but different.. Adv Biol Regul 82:100817 PMID: 34216856
- 6. Kofuji S et al.. 2015. INPP4B Is a PtdIns(3,4,5)P3 Phosphatase That Can Act as a Tumor Suppressor.. Cancer Discov 5(7):730-9 PMID: 25883023
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