Protein Kinase Regulation and GTPase Signaling

Endogenous tracking reveals paralog-specific targets for phosphatidic acid generation during phospholipase C signaling in living cells

The paper investigates paralog-specific effects of DGK inhibitors on PA generation during PLC signaling in live cells, finding that BMS-502 inhibits PA production while R59022 paradoxically increases it.

Functional characterization of Rho GTPase activating proteins SYDE1 and SYDE2

This study characterizes SYDE1 and SYDE2 as JNK substrates with GAP activity toward RhoA, Rac1, and Cdc42, and shows their role in cell morphology and migration.

Changes in the Transcriptome and Synthetic Lethal Dependencies Following KRAS Mutant Expression Reveal Profound Tissue-Specificity

This paper identifies tissue-specific synthetic lethal dependencies driven by KRAS mutations across different cell lineages, revealing distinct genetic vulnerabilities shaped by the tissue context.

Phosphorylation Protects Oncogenic RAS from LZTR1-Mediated Degradation

This study identifies phosphorylation as a mechanism protecting oncogenic RAS from LZTR1-mediated degradation, with implications for targeting RAS stability in hematologic cancers.

A self-organized signaling hierarchy patterns the cortex during cell repair

The paper investigates how Rho and Cdc42 signaling zones form and polarize during cell repair in Xenopus oocytes, revealing a self-organized mechanism involving protein recruitment at signaling compartment overlaps.

A genetically encoded RhoG FRET biosensor reveals spatially compartmentalized RhoG-Rac1 signaling during cell protrusion

The paper develops a FRET biosensor to visualize RhoG activity in live cells and shows its spatial relationship with Rac1 during protrusion.

Concurrent AXL inhibition enhances RAS and ERK inhibitor efficacy in KRAS-mutant pancreatic and lung cancer

This study shows that combining AXL inhibition with RAS or ERK inhibitors enhances efficacy in KRAS-mutant cancers by overcoming resistance mechanisms.

Molecular determinants of differential substrate selection between the Src family kinases Lck and Src

The paper investigates how Lck and Src kinases differ in their ability to phosphorylate ITAMs, identifying structural and conformational differences that underlie their substrate specificity.

A chemical-genetic approach for stress-independent activation of the fission yeast stress-activated protein kinase pathway

The paper introduces a new yeast strain, SISA4, for sustained Sty1 kinase activation without external stress and demonstrates its utility in studying SAPK pathway effects.

Targeting AXL Overcomes Adaptive Resistance to KRAS Inhibition in KRAS-Driven Cancer

This study identifies AXL as a driver of adaptive resistance to KRAS inhibition and shows that combining AXL and KRAS inhibition improves tumor control and immune response in lung and pancreatic cancer models.

Human TBC1 domain-containing kinase is a class I multidomain pseudokinase

The paper characterizes human TBCK as a class I pseudokinase through biochemical and biophysical analysis, revealing its catalytically inactive nature and structural features.

Small molecule activation of the tumor suppressor kinase LKB1

This study develops small molecules that activate the tumor suppressor kinase LKB1 and shows their therapeutic benefits in cancer cell lines.

Loss of Copine D Leads to Ras Activation in Dictyostelium discoideum

This study shows that loss of Copine D in Dictyostelium discoideum increases Ras activation, leading to developmental and cellular changes similar to those seen in cancer.

How Functional Variants Reconfigure the Rac2 Conformational Landscape

This study investigates how mutations in Rac2 alter its conformational dynamics and signaling, revealing distinct inactive and overactive states that impact cellular function.

RASAL3 regulates RAC/CDC42 GTPases, SAPK/JNK signaling, IL-2 gene activity, and directed motility in human T cells

This study investigates RASAL3's role in human T cells, showing it regulates GTPases, signaling pathways, and motility, with implications for improving CAR-T cell therapy.

PLCβs are recruited to the plasma membrane in macrophages by both Gβγ and Gαq

This study shows that PLCβ3 is recruited to the plasma membrane by both Gβγ and Gq in macrophages, revealing dual mechanisms for G protein-dependent regulation of PLCβ enzymes.

Anionic lipids regulate PLCβ membrane recruitment

This study shows that anionic lipids are essential for PLCβ membrane recruitment and modulate Gβγ-dependent activation, highlighting the role of membrane electrostatics in signal transduction.

Deciphering the reciprocal regulation of the Pyk2-Src activation complex

This study investigates how Pyk2 and Src kinases reciprocally regulate each other's activation through phosphorylation and conformational changes.

ARHGAP20 organizes spatial Rap1-RhoA signaling coordination controlling adhesion dynamics during migration

This study identifies ARHGAP20 as a regulator of cell migration by modulating Rap1A-RhoA signaling coordination through vesicular trafficking.

Combinatorial MAPK states drive opposing gene programmes: a reanalysis of MAP3K-driven transcriptional responses in MCF10A cells

The paper reanalyzes RNA-seq data to show that JNK co-activation with ERK drives E2F/MYC transcriptional activation, explaining a 10-fold difference in cell cycle entry compared to ERK-only activation.

Reconstitution of Ras-PI3Kγ membrane communication and feedback using light-induced signaling inputs

This study reconstitutes Ras-PI3Kγ membrane communication and feedback using light-induced signaling inputs, revealing how feedback and diffusion shape spatiotemporal signaling dynamics.

A model for PIP2/3 and Rnd1 effects on Plexin-B1 GAP activity on Rap1b GTPase derived from molecular dynamics simulations

This study uses molecular dynamics simulations to investigate how PIP2/3 and Rnd1 affect Plexin-B1 GAP activity on Rap1b GTPase, revealing lipid-dependent structural and functional changes.

Overcoming Daraxonrasib Resistance: Allele-Specific Mechanisms Guide Salvage Therapy in Pancreatic Cancer

This paper identifies allele-specific resistance mechanisms to daraxonrasib in pancreatic cancer and demonstrates how these guide effective salvage therapies.

Divergent CRD-Dependent Mechanisms Govern RAS Isoform-Selective Recruitment of CRAF and ARAF

This study identifies divergent CRD-dependent mechanisms by which RAS isoforms selectively recruit CRAF and ARAF, revealing how the CRD modulates RAS affinity and RAF activation.

Reversible Opto-Chemical activation of KRASG12V signaling with near single-cell precision

This paper develops a reversible Opto-Chemical system to activate KRASG12V signaling with near single-cell precision and demonstrates its effects on epithelial transformation.

Paradoxical non-catalytic kinase functions are driven by inhibitor-induced displacement of autoinhibitory domains

The paper identifies inhibitor-induced structural changes in kinases that drive non-catalytic effects, revealing the ATP-binding site as a key regulator of kinase conformation and interactions.

Selective knockout of PKA regulatory subunits reveal opposite catalytic and metabolic consequences with implications for Alzheimer's disease

This study shows that knocking out PKA regulatory subunits RI and RII leads to distinct metabolic and phosphorylation changes, with RI KO increasing Tau phosphorylation linked to Alzheimer's disease.

Inducible activation of small GTPases reveals direct effector recruitment and signalling dynamics

This paper introduces SPaRTa, an inducible system to study GTPase-effector interactions, showing that KRAS activation leads to distinct effector recruitment and signaling dynamics.

A new mechanism of regulation of LIM kinases, LIMK1 and LIMK2, modulates their activity on cofilin and actin filament remodelling

The paper identifies a critical amino acid residue that mediates LIMK dimerization and transphosphorylation, essential for their activity on cofilin and actin filament remodeling.

Magnesium as a Conformational Gatekeeper of KRAS: Structural Dynamics and Therapeutic Implications

This study investigates how magnesium regulates KRAS conformational dynamics and nucleotide exchange using HDX-MS and functional assays, revealing Mg2+ as a critical structural stabilizer.