Protein Kinase Regulation and GTPase Signaling

The paper reports 14 co-crystal structures of human IPMK with inhibitors and identifies structural features contributing to inhibitor potency and selectivity.

The paper identifies SPRY2 as a novel K-Ras effector that impacts its membrane organisation through proteomics and BRET screens.

The paper optimizes conditions for GTP loading of H-Ras by evaluating factors like time, temperature, concentration, and mutations to enhance nucleotide exchange efficiency.

This study shows that mono-ubiquitylation of Rap2 is required for its activation and localization to lamellipodia, which regulates actin dynamics and cell migration.

This study presents the cryo-EM structure of PLCε, revealing its N-terminal domains and their role in membrane engagement and activity.

This study characterizes the RAC1P29S mutation in melanoma, showing it hyperactivates signaling pathways by impairing GTP hydrolysis and altering effector interactions.

The study reveals an allosteric mechanism by which the PH domain of ASAP1 enhances Arf1 GTPase activity through structural and dynamic interactions on a membrane surface.

This study identifies a domain-swapped conformation in CaMKII that enables linker-mediated allosteric regulation, demonstrated through structural, computational, and live-cell analyses.

This study identifies how RhoA activates PLCε through a unique EF hand insertion, enhancing membrane interaction and cardiomyocyte survival during ischemia/reperfusion.

The paper identifies an unconventional mechanism where Ca2+-CaM binds CHK2 kinase to inhibit its activity, contrasting with its typical role in promoting kinase activity.

This study screens combinations of RAS pathway inhibitors with targeted agents in patient-derived spheroids with KRAS variants, identifying effective combinations that reduce viability.

This study develops an in vitro BRAF activation assay to elucidate molecular mechanisms of BRAF disassembly and identifies RAS binding as critical for activation.

This paper introduces a method to control small GTPase activity using split-GTPases and user-defined chemical inducers, enabling precise temporal regulation of cellular signaling.

This study identifies oligophosphorylation as a new phosphorylation mode, showing NME1 can catalyze its own oligophosphorylation using ATP, with implications for phosphoregulation.

The paper shows that MAP2Ks can phosphorylate and activate MAPKs using ADP in vitro, suggesting a potential role in maintaining signaling under ATP-depleted conditions.

The paper identifies a regulatory mechanism involving Sty1 and Orb6 kinases that controls Cdc42 dynamics during stress, leading to changes in cell morphology and lifespan.

This study presents the cryo-EM structure of the RalGAP tumor suppressor complex, revealing its tetrameric architecture and providing insights into its function and relevance in cancer.

The paper uses chemical proteomics to analyze KRAS inhibitor effects on signaling networks in cancer cells, revealing cell-specific responses and phosphorylation changes.

The paper identifies a mutation in GGPPS that disrupts inter-dimer interactions, leading to increased substrate affinity and product release, revealing product inhibition as a regulatory mechanism in GGPPS.

This study develops a covalent LIMK1 inhibitor that selectively targets a unique cysteine, enabling isoform-specific studies of LIMK1 function.

The paper investigates the role of RALA S194 phosphorylation in cancer by knocking out RALA and reconstituting it with wild-type and mutant forms, finding that phosphorylation is necessary for tumor formation but not activation.

The paper identifies variants in the TRIO PH2 domain that relieve autoinhibition of GEF2 activity, linking them to neurodevelopmental disorders.

This study identifies PIP4K as a conserved enzyme in early metazoans that regulates growth and development through insulin receptor signaling.

This study investigates how class I PAKs regulate actin cytoskeleton excitability by showing that their kinase activity limits PIP3 production and PI3K activity.

This study identifies the SUMO-interacting motif in EPAC1 as critical for its subcellular targeting and functional regulation, including cAMP binding and signaling microdomain formation.

The paper develops a framework to infer ERK signaling dynamics from fixed-cell immunostains by combining machine learning and differential equations, showing that protein levels reflect different activation timescales.

This study identifies Arl4D as a scaffolding protein that recruits Erk1/2 and Pak1 to the plasma membrane, enabling their phosphorylation and cell migration.

The paper uses optogenetics to control RhoA GEF localization, showing a single protein can induce retraction or protrusion based on its concentration, revealing a signaling switch mechanism.

This paper introduces a fluorescence HPLC-based assay to quantify small GTPase activation states, demonstrating its application in analyzing RHEB and KRAS in cells and tumor models.

This study identifies allosteric factors in the CaMKII hub domain that determine GHB ligand selectivity for CaMKIIa over other isozymes.