Protein Kinase Regulation and GTPase Signaling

This study identifies how the αI-helix modulates Abl kinase activity through mechanical forces affecting the KD/SH2SH3 interface, with implications for drug response.

This paper shows that aPKC phosphorylates Cdc42 to regulate its own asymmetric localization and cell polarity in C. elegans zygotes.

This study identifies PKCdeltaIII, a splicing variant of PKCdelta, as inducing neurite outgrowth in PC12 cells without NGF, distinct from NGF-mediated pathways.

This study reports the cryo-EM structure of LRRK1 and its dimer, revealing structural differences from LRRK2 and providing insights into their regulation.

The paper shows how a single amino acid change in PKCβ's C1A domain can switch between cancer-promoting and neurodegenerative effects by altering autoinhibition and degradation.

The paper generates a deep phosphoproteomics dataset of the EGFR-MAPK pathway in MCF10A cells and integrates it with protein databases to study kinase signaling.

The paper shows that RAS G-domains influence the sorting of phosphatidylserine acyl chains in the plasma membrane, with different mutants sorting distinct PS species.

The paper investigates how distinct hyperactive RAS/MAPK alleles affect cortical GABAergic interneurons, revealing shared molecular programs and a role for increased neural activity in altering interneuron subtypes.

The paper predicts Ras-effector binding affinities using structural models and identifies mutations that alter binding energy, providing insights into rewiring Ras interactions.

The paper develops a model to predict KRAS dependency using molecular profiles from cell lines, achieving high accuracy in validation and external datasets.

The paper evaluates all possible CXXX sequences as farnesyltransferase targets in yeast using a reporter system, revealing expanded specificity beyond the canonical CaaX motif.

This paper describes the design of a lipid-based drug, LIG1, that targets KRAS4B-G12D and phosphodiesterase-delta to inhibit cancer cell proliferation.

This study shows that Grb2 enhances PIP3-bound Btk activity on membranes by recruiting it to scaffold-mediated signaling clusters.

The paper identifies context-specific KRAS-effectors in Caco-2 cells and shows that culture contexts have a larger impact on interaction rewiring than genetic contexts.

This study identifies two distinct mechanisms by which Crk proteins activate C3G: adaptor-dependent interactions with specific motifs and phosphorylation-dependent priming.

This study identifies Inka2 as a Pak4 inhibitor that regulates actin dynamics in neuronal development by promoting depolymerization and inhibiting protrusion formation.

This study evaluates K-Ras4B dimer interfaces and finds that Raf effectors stabilize dimers on the membrane, identifies a dynamic water channel, and suggests modulating membrane interactions as a potential therapeutic strategy.

This study shows that the atypical MAPK Erk2 regulates GtaC translocation in response to chemoattractants, revealing a mechanism for MAPK-mediated transcription factor regulation.

The paper develops engineered kinases to specifically phosphorylate fluorescent protein fusions in vivo, demonstrating their use in studying actomyosin activation in Drosophila embryos.

The paper identifies Smog as a GPCR that transduces Fog signals to regulate Rho kinase and myosin activation during Drosophila salivary gland invagination, revealing its role in apical constriction and epithelial integrity.

The paper uses optogenetic actuator and ERK biosensor circuits to study MAPK network dynamics and identifies RSK2-mediated feedback as critical for ERK regulation and drug response.

The paper develops a kinase translocation reporter to monitor ERK activity in real-time in Drosophila and identifies novel dynamics in ERK signaling during development.

The paper classifies over 700 RAS structures into conformations based on SW1 and SW2 loops, identifies mutation impacts, and creates a database for analysis.

The paper analyzes LZTR1 loss-of-function mutants in fruit flies and mice, showing dependency on RIT1 orthologs and haplosufficiency in mice.

This paper designs a CDC42 effector interaction inhibitor (ARN22089) that shows anti-cancer activity by blocking tumor invasion and angiogenesis.

The paper shows that PKA-R translocation to the plasma membrane can both enhance and inhibit kinase activity depending on concentration, affecting cell migration directionality.

This study compares the structure, function, and high-order assembly of neuronal CaMKII and β-isoforms using single-particle EM and biochemical methods, revealing differences in their extended states and clustering behavior.

The paper shows KRAS mutations disrupt its interaction with LZTR1, affecting protein stability via the CUL3 ubiquitin ligase complex, contributing to oncogenesis.

The paper investigates how the GTPase Ran/Gsp1 achieves functional multi-specificity through biophysical and genetic perturbations, revealing that its effects are linked to kinetic parameters of the switch cycle rather than direct interaction sites.