Biology subjects

Hammond, G. R.

Publications and source records attributed to Hammond, G. R..

At least 19 recordsLinked to original sources

bioRxiv2026

The proximal lipid phase of PI3K signaling is confined to the plasma membrane

Class I phosphoinositide 3-kinases (PI3Ks) generate the lipid second messengers PIP3 and PI(3,4)P2 to control diverse cellular processes including growth, metabolism, and survival. Although these signals are classically thought to arise at the plasma membrane, several recent studies have proposed that PI3K signaling is propagated from intracellular membranes along the endocytic pathway. Here, we combined genomic tagging of endogenous PI3K pathway enzymes with single-molecule imaging and sensitive lipid biosensors to define the spatial organization of PI3K signaling in living cells. We find that PI3K catalytic subunits are recruited to the plasma membrane but do not undergo detectable endosomal translocation during receptor activation. Consistently, PIP3 and PI(3,4)P2 accumulation is restricted to the plasma membrane, despite enrichment of lipid phosphatases along the endocytic pathway. Functional perturbation experiments further show that degradation of PI(3,4)P2 occurs predominantly at the plasma membrane, indicating that both synthesis and termination of proximal lipid signals are spatially confined to this compartment. Together, these results resolve the subcellular localization of proximal PI3K signaling and support a model in which lipid second messenger production is restricted to the plasma membrane, with diversification of downstream pathway outputs occurring through redistribution of activated effector proteins rather than intracellular propagation of lipid signals.

cell biology↗

bioRxiv2026

In Cellulo pharmacological profiling and genomic editing reveals paralog-specific targets for PA generation during PLC signaling

Phosphatidic acid (PA) is an essential intermediate generated during phospholipase C (PLC) signaling, but its regulation is complex. PA can be generated by ten different diacylglycerol kinase paralogs (DGKs) and two different phospholipase D paralogs (PLDs) in mammals. Because these enzymes are activated under diverse conditions and at various membranes, understanding paralog-specific contributions to PA production is critical for therapeutic development of drugs that modulate the PLC pathway. To address this, we aimed to characterize the paralog specificity of the DGK inhibitors R59022 and BMS-502 against individual endogenously-tagged DGK paralogs in live cells. We found that R59022 and BMS-502 both recruited endogenous DGKalpha to the plasma membrane, and inhibited the catalytic fragment of DGKalpha when ectopically localized to the mitochondrial outer membrane. However, at its effective dose, R59022 paradoxically increased PA levels, while BMS-502 functioned as a potent inhibitor. Live-cell imaging experiments using BMS-502 with carbachol stimulation of endogenous muscarinic receptors showed that inhibition of both DGKalpha and the PLDs is needed to substantially reduce PA levels during PLC activation. Our findings both identify paralog-specific druggable targets for modulating PLC signaling events, and establish a new platform for characterizing DGK and PLD activity in living cells.

biochemistry↗

bioRxiv2025

Molecular insights into Profilin1-dependent regulation of cellular phosphatidylinositol-(4,5)-bisphosphate

Phosphatidylinositol (4,5)-bisphosphate (PIP2), the most abundant cellular poly-phosphoinositide (PPI) class of phospholipid, is a central plasma membrane (PM)-associated signaling hub that controls many cellular processes. In this study, we demonstrate that either deletion of the gene encoding actin-binding protein profilin1 (Pfn1) or disruption of Pfn1-actin interaction leads to downregulation of PM PIP2 content in cells. This is also phenocopied when F-actin is depolymerized implying that Pfn1-dependent PIP2 alteration is related to its actin-regulatory function. Phospholipase C (PLC) activity is critical for Pfn1-deficient cells to exhibit the PIP2-related phenotype. These findings, taken together with biochemical signatures of elevated PIP2 hydrolysis (higher baseline PM diacylglycerol-to PIP2 ratio and protein kinase C activity) exhibited by Pfn1-deficient cells, imply that PLC-mediated PIP2 hydrolysis plays a role in Pfn1-dependent regulation of PM PIP2. Furthermore, we unexpectedly found that Pfn1 loss leads to dramatic alterations in several other important forms of lipids, revealing a previously unrecognized role of Pfn1 as a broad regulator of cellular lipid environment that extends beyond PPI control. In conclusion, our study establishes Pfn1 as an important regulator of cellular lipid homeostasis. SUMMARY STATEMENTThis study uncovers a mechanism of how functional loss of Profilin1, a key regulator of actin cytoskeleton, can trigger downregulation of plasma membrane content of PIP2, an important class of phospholipid, in cells.

cell biology↗

bioRxiv2025

Stereoselective Degradation of Diacylglycerol Kinases Potentiate T cell Activation and Tumor Cell Cytotoxicity

Stereoselective recognition is a powerful means to differentiate selective versus non-specific activity of small molecules in complex biological systems. Here, we disclose stereochemically defined, sulfonyl-triazole inhibitors of the lipid enzyme diacylglycerol kinase-alpha (DGK), a key metabolic checkpoint for T cell effector function. Acute treatment with the covalent DGK inhibitor AHL-7160 recruited endogenous DGK to the plasma membrane in a stereoselective and isozyme-specific manner. The membrane translocation activity of AHL-7160 correlated with blockade of cellular phosphatidic acid production and potentiation of primary T cell-mediated killing of a glioblastoma cell line. Quantitative chemoproteomics revealed Y669 and K411 as sites of AHL-7160 modification on endogenous DGK in cells. Extended treatments resulted in proteasome-dependent and proteome-wide selective degradation of DGK in T cells. Collectively, these findings establish covalent DGK ligands as potent molecular glues with translational potential in immunotherapy.

biochemistry↗

bioRxiv2025

Independent validation of the SnxA biosensor as a sensitive reporter of PI(3,5)P2 dynamics

PI(3,5)P2 is an endosomal lipid whose depletion is associated with a variety of pathologies such as neurodegenerative diseases. However, studying this lipid in physiological and disease models has been difficult due to the scarcity of the lipid and the lack of live-cell imaging tools. That is until recently, when a novel PI(3,5)P2 biosensor, SnxA, was characterized. Despite the exciting promise of this new sensor, it was still unclear if SnxA unbiasedly reported on PI(3,5)P2 levels and how its sensitivity compared to other PI(3,5)P2 biosensors. In this work, we addressed these gaps by using a recruitable PIKfyve construct to demonstrate that ectopically generated PI(3,5)P2 at mitochondria was sufficient to recruit SnxA. Further, we co-expressed putative PI(3,5)P2 biosensors to definitively show that SnxA is more sensitive to PI(3,5)P2. We also validated previous results by showing that SnxA depends on PI(3,5)P2 for membrane binding, SnxA responds to PI(3,5)P2 production at endosomes, and that PI(3,5)P2 levels decline quickly when its production is inhibited. Thus, we conclude that SnxA is a robust and sensitive PI(3,5)P2 biosensor that facilitates real-time analysis of this key lipid.

cell biology↗

bioRxiv2025

PIP4K attenuates PIP5K lipid kinase activity by disrupting membrane-mediated dimerization

The phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family of enzymes generate most of the phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) lipids in eukaryotes. In solution, PIP5K exists in a weak monomer-dimer equilibrium but undergoes membrane-mediated dimerization, which potentiates lipid kinase activity. In vivo, however, PI(4,5)P2 levels are held remarkably constant due to the homeostatic regulation of PIP5K by PIP4K. We hypothesized that mechanisms that regulate PIP5K dimerization could function to buffer lipid kinase activity, thus providing a mechanism for maintaining relatively constant PI(4,5)P2 levels at the plasma membrane. Due the transient nature and density dependence of PIP5K dimerization, deciphering how other proteins modulate PIP5K dimerization has not been feasible. To address this limitation, we established a single molecule FRET assay to visualize membrane-mediated homodimerization and heterodimerization of PIP5K paralogs on supported lipid bilayers using Total Internal Reflection Fluorescence Microscopy (TIRF-M). Using this approach, we find that PIP4K attenuates PIP5K lipid kinase activity by disrupting membrane-mediated dimerization. Guided by structure prediction, we generated PIP4K mutants that are unable to disrupt PIP5K membrane-mediated dimerization thus preventing the attenuation lipid kinase activity. In vivo, mutations that disrupt the PIP4K-PIP5K interaction similarly prevent PIP4K-mediated inhibition of the PIP5K activity. Overall, this work reveals the molecular basis of the PIP4K-mediated inhibition of PIP5K, which underlies PI(4,5)P2 lipid homeostasis. Creation of this PIP5K dimerization FRET biosensor also establishes a novel tool for deciphering how proteins modulate membrane-mediated dimerization of PIP5K in the future.

biochemistry↗

bioRxiv2024

Single molecule Lipid Biosensors Mitigate Inhibition of Endogenous Effector Proteins

Genetically encoded lipid biosensors uniquely provide real time, spatially resolved kinetic data for lipid dynamics in living cells. Despite clear strengths, these tools have significant drawbacks; most notably, lipid molecules bound to biosensors cannot engage with effectors, potentially inhibiting signaling. Here, we show that although PI 3-kinase (PI3K)-mediated activation of Akt is not significantly reduced in a cell population transfected with a PH-Akt1 PIP3/PI(3,4)P2 biosensor, single cells expressing PH-Akt at visible levels have reduced activation. Tagging endogenous AKT1 with neonGreen reveals its EGF-mediated translocation to the plasma membrane. Co-transfection with the PH-Akt1 or other PIP3 biosensors eliminates this translocation, despite robust recruitment of the biosensors. Inhibition is even observed with PI(3,4)P2-selective biosensor. However, expressing lipid biosensors at low levels, comparable with those of endogenous AKT, produced no such inhibition. Helpfully, these single-molecule biosensors revealed improved dynamic range and kinetic fidelity compared with over-expressed biosensor. This approach represents a non-invasive way to probe spatiotemporal dynamics of PI3K signaling in living cells. eTOC summaryHolmes and colleagues show that AKT activation is blocked by commonly used PIP3 biosensors, but that this can be overcome by expressing biosensors at single molecule levels - which also improves kinetic fidelity and sensitivity.

cell biology↗

bioRxiv2024

Nir1-LNS2 is a novel phosphatidic acid biosensor that reveals mechanisms of lipid production

Despite various roles of phosphatidic acid (PA) in cellular functions such as lipid homeostasis and vesicular trafficking, there is a lack of high-affinity tools to study PA in live cells. After analyzing the predicted structure of the LNS2 domain from the lipid transfer protein Nir1, we suspected that this phosphatidic acid-interacting Lipin-like sequence of Nir1 (PILS-Nir1) could serve as a novel PA biosensor. We then performed liposome binding assays as well as pharmacological and genetic manipulations of HEK293A cells expressing a fluorescent PILS-Nir1 to determine how specific lipids affect the interaction of PILS-Nir1 with membranes. We found that PILS-Nir1 bound to both PA and PIP2 in vitro. However, only PA was necessary and sufficient to localize PILS-Nir1 to membranes in cells. PILS-Nir1 also showed a heightened responsiveness to PA produced in various organelles when compared to biosensors using the Spo20 PA binding domain. PILS-Nir1s high sensitivity revealed a modest but discernible contribution of PLD to PA production downstream of muscarinic receptors, which has not been visualized with previous Spo20-based probes. In summary, PILS-Nir1 emerges as a versatile and sensitive biosensor, offering a new powerful tool for real-time investigation of PA dynamics in live cells.

cell biology↗

bioRxiv2024

Myotubularin-related proteins regulate KRAS function by controlling plasma membrane levels of polyphosphoinositides and phosphatidylserine

KRAS, a small GTPase involved in cell proliferation and differentiation, frequently gains activating mutations in human cancers. For KRAS to function, it must bind the plasma membrane (PM) via interactions between its membrane anchor and phosphatidylserine (PtdSer). Therefore, depleting PM PtdSer abrogates KRAS PM binding and activity. From a genome-wide siRNA screen to identify genes regulating KRAS PM localization, we identified a set of phosphatidylinositol (PI) 3-phosphatases: myotubularin-related proteins (MTMR) 2, 3, 4, and 7. Here, we show that silencing MTMR 2/3/4/7 disrupts KRAS PM interactions by reducing PM PI 4-phosphate (PI4P) levels, thereby disrupting the localization and operation of ORP5, a lipid transfer protein maintaining PM PtdSer enrichment. Concomitantly, silencing MTMR 2/3/4/7 elevates PM PI3P levels while reducing PM and total PtdSer levels. We also observed MTMR 2/3/4/7 expression is interdependent. We propose that the PI 3-phosphatase activity of MTMR is required for generating PM PI, necessary for PM PI4P synthesis, promoting the PM localization of PtdSer and KRAS. eTOC summaryWe discovered that silencing the phosphatidylinositol (PI) 3-phosphatase, MTMR, disrupts the PM localization of PtdSer and KRAS. We propose a model, where MTMR loss depletes PM PI needed for PM PI4P synthesis, an essential phospholipid for PM PtdSer enrichment, thereby impairing KRAS PM localization.

cell biology↗

bioRxiv2023

OSBP is a major determinant of Golgi phosphatidylinositol 4-phosphate homeostasis

The lipid phosphatidylinositol 4-phosphate (PI4P) plays a master regulatory role at Golgi membranes, orchestrating membrane budding, non-vesicular lipid transport and membrane organization. It follows that harmonious Golgi function requires strictly maintained PI4P homeostasis. One of the most abundant PI4P effector proteins is the oxysterol binding protein (OSBP), a lipid transfer protein that exchanges trans Golgi PI4P for ER cholesterol. Although this protein consumes PI4P as part of its lipid anti-porter function, whether it actively contributes to Golgi PI4P homeostasis has been questioned. Here, we employed a series of acute and chronic genetic manipulations, together with orthogonal targeting of OSBP, to interrogate its control over Golgi PI4P abundance. Modulating OSBP levels at ER:Golgi membrane contact sites produces reciprocal changes in PI4P levels. Additionally, we observe that OSBP has a high capacity for PI4P turnover, even at orthogonal organelle membranes. However, despite also visiting the plasma membrane, endogenous OSBP makes no impact on PI4P levels in this compartment. We conclude that OSBP is a major determinant of Golgi PI4P homeostasis.

cell biology↗

bioRxiv2023

Orthogonal targeting of SAC1 to mitochondria implicates ORP2 as a major player in PM PI4P turnover

Oxysterol binding protein (OSBP)-related proteins (ORPs) 5 and 8 have been shown to deplete the lipid phosphatidylinositol 4-phosphate (PI4P) at sites of membrane contact between the endoplasmic reticulum (ER) and plasma membrane (PM). This is believed to be caused by transport of PI4P from the PM to the ER, where PI4P is degraded by an ER-localized SAC1 phosphatase. This is proposed to power the anti-port of phosphatidylserine (PS) lipids from ER to PM, up their concentration gradient. Alternatively, ORPs have been proposed to sequester PI4P, dependent on the concentration of their alternative lipid ligand. Here, we aimed to distinguish these possibilities in living cells by orthogonal targeting of PI4P transfer and degradation to PM-mitochondria contact sites. Surprisingly, we found that orthogonal targeting of SAC1 to mitochondria enhanced PM PI4P turnover independent of targeting to contact sites with the PM. This turnover could be slowed by knock-down of soluble ORP2, which also has a major impact on PM PI4P levels even without SAC1 over-expression. The data reveal a role for contact site-independent modulation of PM PI4P levels and lipid antiport.

cell biology↗

bioRxiv2023

Missense mutations in the calcium-activated chloride channel TMEM16A promote tumor growth by activating oncogenic signaling in Human Cancer.

The calcium-activated chloride channel TMEM16A is overexpressed in several tumors. This condition is associated with a poor survival prognosis but highlights TMEM16As potential as a biomarker and target for anti-cancer therapies. Numerous somatic mutations of TMEM16A have been reported; however, their potential and molecular mechanism of oncogenesis are unknown. Here, we investigate the function and oncogenicity of nine-point mutations found in human cancerous tissues (R451P, R455Q, M546I, R557W, F604L, D902N, K913E, D914H, and Q917K). These mutations are located on the extracellular side and near the third Ca2+-binding site, near a PtdIns(4,5)P2 site in the human TMEM16A channel. Our findings reveal that these mutations affected gating, Ca2+ sensitivity, phosphorylation of essential signaling proteins, cell proliferation, and tumor growth. Notably, R451P and D902N exhibit low Ca2+ sensitivity, yet their overexpression promotes phosphorylation of EGFR and AKT, as well as in vivo tumorigenesis, without Ca2+-enhancing stimuli. Conversely, the charged-neutralizing mutation R451Q and the conservative mutation D902E restored Ca2+ sensitivity and altered cell proliferation and tumor growth as wild-type did. Thus, we conclude that the oncogenic phenotype of TMEM16A missense mutations is independent of chloride flux but involves the differential activation of cell signaling components associated with cell proliferation.

cancer biology↗

bioRxiv2022

Depletion of Plasma Membrane PI4P by ORP5 Requires Hydrolysis by SAC1 in Acceptor Membranes

The authors have withdrawn their manuscript because the central conclusion is incorrect. We discovered this while revising the paper after peer review. In the original submission, we described ectopic targeting of the PI4P transfer protein, ORP5. We reported that when combined with orthogonal targeting of SAC1 to the mitochondrial outer membrane, ORP5 facilitates depletion of PM PI4P when targeted to PM-mitochondria contact sites. New experiments revealed that orthogonal targeting of SAC1 to the mitochondria alone is sufficient to deplete PM PI4P; ORP5 is not required. Thus, although the data reported in the manuscript are valid and reproducible, the conclusion was incorrect. We are currently performing additional experiments to better characterize and understand the effects of mitochondrially-targeted SAC1 on PM pools of PI4P. We will post a new manuscript detailing these findings on bioRXiv, which will be submitted for peer review at the original journal as a revision. In the meantime, we are withdrawing the preprint so as not to mislead the field with the erroneous conclusion. We sincerely apologize to anyone whose work was misdirected by our honest mistake. Therefore, the authors do not wish this work to be cited as reference for the project in its present form. If you have any questions, please contact the corresponding author.

cell biology↗

bioRxiv2022

A Novel Homeostatic Mechanism Tunes PI(4,5)P2-dependent Signaling at the Plasma Membrane

The lipid molecule phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2) controls all aspects of plasma membrane (PM) function in animal cells, from its selective permeability to the attachment of the cytoskeleton. Although disruption of PI(4,5)P2 is associated with a wide range of diseases, it remains unclear how cells sense and maintain PI(4,5)P2 levels to support various cell functions. Here, we show that the PIP4K family of enzymes that synthesize PI(4,5)P2 via a minor pathway, also function as sensors of tonic PI(4,5)P2 levels. PIP4Ks are recruited to the PM by elevated PI(4,5)P2 levels, where they inhibit the major PI(4,5)P2-synthesizing PIP5Ks. Perturbation of this simple homeostatic mechanism reveals differential sensitivity of PI(4,5)P2-dependent signaling to elevated PI(4,5)P2 levels. These findings reveal that a subset of PI(4,5)P2-driven functions may drive disease associated with disrupted PI(4,5)P2 homeostasis. One-Sentence SummaryThe enzyme PIP4K functions as both a sensor and negative regulator of PI(4,5)P2 synthesis by the closely related PIP5K enzymes, tuning the activity of numerous membrane functions.

cell biology↗

bioRxiv2022

PtdIns(3,4)P2, Lamellipodin, and VASP coordinate cytoskeletal remodeling during phagocytic cup formation in macrophages.

Phosphoinositides are pivotal regulators of vesicular traffic and signaling during phagocytosis. Phagosome formation, the initial step of the process, is characterized by local membrane remodelling and reorganization of the actin cytoskeleton that leads to formation of the pseudopods that drive particle engulfment. Using genetically-encoded fluorescent probes we found that upon particle engagement a localized pool of PtdIns(3,4)P2 is generated by the sequential activities of class I phosphoinositide 3-kinases and phosphoinositide 5-phosphatases. Depletion of the enzymes responsible for this locally generated pool of PtdIns(3,4)P2 blocks pseudopod progression and ultimately phagocytosis. We show that the PtdIns(3,4)P2 effector Lamellipodin (Lpd) is recruited to nascent phagosomes by PtdIns(3,4)P2. Furthermore, we show that silencing of Lpd inhibits phagocytosis and produces aberrant pseudopodia with disorganized actin filaments. Lastly, vasodilator-stimulated phosphoprotein (VASP) was identified as a key actin-regulatory protein mediating phagosome formation downstream of Lpd. Mechanistically, our findings imply that a pathway involving PtdIns(3,4)P2, Lpd and VASP mediates phagocytosis at the stage of particle engulfment.

cell biology↗

bioRxiv2022

Dynamic Turnover of PI4P and PI(4,5)P2 under Hypoxia Controls Electrostatic Plasma Membrane Targeting

Phosphatidylinositol 4-phosphate (PI4P) and phosphatidylinositol 4,5-biphosphate (PIP2) are key phosphoinositides that determine the identity of the plasma membrane (PM) and regulate numerous key biological events there. To date, mechanisms regulating the homeostasis and dynamic turnover of PM PI4P and PIP2 in response to various physiological conditions and stresses remain to be fully elucidated. Here we report that hypoxia in Drosophila induces acute and reversible depletion of PM PI4P and PIP2 that severely disrupts the electrostatic PM targeting of multiple polybasic polarity proteins. Genetically encoded ATP sensors confirmed that hypoxia induces acute and reversible reduction of cellular ATP levels which showed a strong real-time correlation with the levels of PM PI4P and PIP2 in cultured cells. By combining genetic manipulations with quantitative imaging assays we showed that PI4KIII, as well as Rbo/EFR3 and TTC7 that are essential for targeting PI4KIII to PM, are required for maintaining the homeostasis and dynamic turnover of PM PI4P and PIP2 under normoxia and hypoxia. Our results revealed that in cells challenged by energetic stresses triggered by hypoxia, ATP inhibition and possibly ischemia, dramatic turnover of PM PI4P and PIP2 could have profound impact on many cellular processes including electrostatic PM targeting of numerous polybasic proteins.

cell biology↗

bioRxiv2022

Free diffusion of PI(4,5)P2 in the plasma membrane in the presence of high density effector protein complexes

The lipid phosphatidyl-D-myo-inositol-4,5-bisphosphate [PI(4,5)P2] is a master regulator of plasma membrane (PM) function. It engages effector proteins that regulate diverse traffic, transport, signaling and cytoskeletal processes that define PM structure and function. How a single class of lipid molecules independently regulate so many parallel processes remains an open question. We tested the hypothesis that spatially segregated pools of PI(4,5)P2 are associated with, and thus reserved for regulation of, different functional complexes in the PM. The mobility of PI(4,5)P2 in the membrane was measured using lipid biosensors by single particle tracking photoactivation localization microscopy (sptPALM). We found that PI(4,5)P2, and several other classes of inner PM lipids, diffuse rapidly at approximately 0.3 {micro}m2/s with largely Brownian motion, although they spend approximately a third of their time diffusing much more slowly. Surprisingly, areas of the PM occupied by PI(4,5)P2-dependent complexes, such endoplasmic-reticulum:PM contact sites, clathrin-coated structures, and several actin cytoskeletal elements including focal adhesions, did not cause a change in PI(4,5)P2 lateral mobility. Only the spectrin and septin cytoskeletons were observed to produce a slowing of PI(4,5)P2 diffusion. We conclude that even structures with high densities of PI(4,5)P2-engaging effector proteins, such as clathrin coated pits and focal adhesions, do not corral free PI(4,5)P2, questioning a role for spatially segregated PI(4,5)P2 pools in organizing and regulating parallel PM functions.

cell biology↗

bioRxiv2021

Phosphatidylinositol 3-kinase-independent synthesis of PtdIns(3,4)P2 by a phosphotransferase

Despite their comparatively low abundance, phosphoinositides play a central role in membrane traffic and signalling. PtdIns(3,4,5)P3 and PtdIns(3,4)P2 are uniquely important, as they promote cell growth, survival, and migration. Pathogenic organisms have developed means to subvert phosphoinositide metabolism to promote successful infection and their survival within host organisms. We demonstrate that PtdIns(3,4)P2 is generated in host cells by effectors of the enteropathogenic bacteria Salmonella and Shigella. Pharmacological, gene silencing and heterologous expression experiments revealed that, remarkably, the biosynthesis of PtdIns(3,4)P2 occurs independently of phosphoinositide 3-kinases. Instead, we found that the Salmonella effector SopB, heretofore believed to be a phosphatase, generates PtdIns(3,4)P2 de novo via a phosphotransferase/phosphoisomerase mechanism. Recombinant SopB is capable of generating PtdIns(3,4)P2 from PtdIns(4,5)P2 in a cell-free system. Through a remarkable instance of convergent evolution, bacterial effectors acquired the ability to synthesize 3-phosphorylated phosphoinositides by an ATP- and kinase-independent mechanism, thereby subverting host signaling to gain entry and even provoke oncogenic transformation.

cell biology↗