Protein Tyrosine Phosphatases

Phosphatase SHP2 pathogenic mutations enhance activity by altering conformational sampling

This study investigates how pathogenic mutations in SHP2's SH2 domains alter conformational dynamics, leading to hyperactivation by stabilizing a zipped β-sheet state.

Phospho-proteomics identifies D-group MAP kinases as substrates of the Arabidopsis tyrosine phosphatase RLPH2

Phospho-proteomic analysis reveals Arabidopsis tyrosine phosphatase RLPH2 dephosphorylates the activation loop of D-Group mitogen activated protein kinases.

Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants

This study uses proximity-labeling proteomics to analyze how SHP2 mutations alter its interactome and localization, revealing functional consequences of different mutation types.

Mechanism of SHP2 activation by bis-Tyr-phosphorylated Gab1

This study identifies how bis-Tyr-phosphorylated Gab1 activates SHP2 by binding both SH2 domains and inducing structural changes.

PTPRJ-Targeting Peptide Agonist Induces Broad Cellular Signaling Perturbations and DNA Damage in Lung Cancer Cells

This study evaluates a PTPRJ-targeting peptide agonist's effects on lung cancer cells, revealing broad signaling changes, DNA damage, and growth inhibition.

The pathogenic E139D mutation stabilizes a non-canonical active state of the multi-domain phosphatase SHP2

This study identifies a novel active conformation of SHP2 stabilized by the E139D mutation, which alters phosphoprotein binding preferences compared to canonical hyperactive mutants.

Ionizable networks mediate pH-dependent allostery in SH2 signaling proteins

This paper investigates how pH dynamics regulate SH2 signaling proteins like SHP2 and Src through allosteric mechanisms involving ionizable networks.

Structures of human PTP1B variants reveal allosteric sites to target for weight loss therapy

The paper identifies functional PTP1B variants in thin individuals and uses structural biology to reveal allosteric sites for obesity drug development.

Inhibition of SHP-1 /2 blocks antigen cross-presentation by human macrophages and dendritic cells

This study shows that inhibiting SHP-1/2 reduces antigen cross-presentation by macrophages and dendritic cells, potentially limiting the effectiveness of PD-1 checkpoint therapy.

ASPPs multimerize protein phosphatase 1

The paper shows ASPPs multimerize PP1 to form phosphatase hubs at cell-cell junctions, and mutant ASPPs disrupt this oligomerization, which can be rescued by forcing PP1 clustering.

SH2-mediated steric occlusion of the C2 domain regulates autoinhibition of SHIP1 inositol 5-phosphatase

This study identifies how the SH2 domain sterically occludes the C2 domain to autoinhibit SHIP1, revealing structural and functional relationships critical for its membrane localization and phosphatase activity.

Oncogenic PTPN11/SHP2 drives immune escape in juvenile myelomonocytic leukemia (JMML) through activation of ectonucleotidase/adenosine signaling

This study identifies PTPN11/SHP2-driven adenosine signaling as a mechanism of immune escape in JMML, showing that CD39 inhibition can enhance T cell responses and reduce myeloproliferation.

Dynamic and structural insights into allosteric regulation on MKP5 a dual-specificity phosphatase

This study investigates the allosteric regulation of MKP5 by identifying the role of residue Y435 in maintaining the structural integrity of the allosteric pocket and its interaction with p38 MAPK and JNK.

The phosphatases TCPTP, PTPN22, and SHP1 play unique roles in T cell phosphotyrosine maintenance and feedback regulation of the TCR

This study investigates the roles of TCPTP, PTPN22, and SHP1 in T cell phosphotyrosine regulation and TCR signaling using CRISPR/Cas9 and mass spectrometry, revealing distinct effects on pY levels and Erk1/2 feedback.

T Lymphocyte-Specific Deletion of SHP1 and SHP2 Promotes Activation-Induced Cell Death of CD4+ T Cells and Impairs Antitumor Response

This study shows that deleting SHP1 and SHP2 in T cells increases CD4+ T cell activation-induced cell death and reduces antitumor responses, with SHP2 loss enhancing anti-PD-1 therapy.

Targeting of PTP4A3 overexpression sensitises HGSOC cells towards chemotherapeutic drugs.

This study shows that targeting PTP4A3 in HGSOC cells can sensitize them to chemotherapeutic drugs, especially when combined with pan-PTP4A inhibition.

Three STEPs forward: A trio of unexpected structures of PTPN5

This study presents three new crystal structures of STEP (PTPN5) revealing unexpected conformational features and ligand binding events that provide insights for structure-based drug design.

Deep mutational scanning of a multi-domain signaling protein reveals mechanisms of regulation and pathogenicity

The paper uses deep mutational scanning to analyze SHP2 mutations, revealing diverse regulatory mechanisms and potential pathogenicity of uncharacterized variants.

Phosphatase activity is dispensable for PRL-3-mediated oncogenesis and tumor progression

This study shows PRL-3 promotes cancer without needing its phosphatase activity, using zebrafish and cell line models, and suggests targeting its protein interactions as a therapy.

A Literature Review and Pooled Case Analysis of Cardiofaciocutaneous Syndrome to Estimate Cancer Risk

This paper reviews literature and analyzes case data to estimate cancer risk in Cardiofaciocutaneous Syndrome (CFC) patients, finding elevated but limited cancer risk in early childhood.

PHLPP2 is a pseudophosphatase that lost activity in the metazoan ancestor

This study reveals that PHLPP2 is a pseudophosphatase with no catalytic activity, challenges its role as a tumor suppressor, and identifies its non-catalytic functions in Akt signaling.

Identification of Small Molecule Inhibitors of PPM1D Using a Novel Drug Discovery Platform

This study identifies new PPM1D inhibitors using a drug discovery platform and shows their distinct biological effects compared to other DDR and p53 pathway modulators.

A functional map of phosphoprotein phosphatase regulation identifies an evolutionary conserved reductase for the catalytic metal ions

The paper identifies CYB5R4 as an evolutionarily conserved reductase that activates PP4 and PP6 by reducing their catalytic metal ions, essential for cell viability under oxidative stress.

Identification of DOK2 and PTPN11 as novel interactors of T cell specific adapter protein TSAd

This study identifies DOK2 and PTPN11 as novel interactors of TSAd using AP-MS, revealing their role in negative T cell signaling.

A Drosophila model for Costello Syndrome caused by Ras mutation K117R

This paper characterizes the Drosophila model of Costello Syndrome caused by the rare HRas K117R mutation, showing increased lethality, reduced body size, and specific phenotypes that suggest distinct roles for Raf-ERK and PI3K signaling pathways.

Allosteric inhibition rescues hydrocephalus caused by catalytically inactive Shp2

This study shows that a catalytically inactive Shp2 mutation causes hydrocephalus by altering conformation, which can be rescued by allosteric inhibition.

DUSP12 promotes cell cycle progression and protects cells from cell death by regulating ZPR9

This study identifies ZPR9 as a DUSP12 interactor and shows DUSP12 promotes cell cycle progression and protects cells from stress-induced apoptosis by de-phosphorylating ZPR9.

Dual-Action Kinase Inhibitors Influence p38α MAP Kinase Dephosphorylation

The paper identifies dual-action kinase inhibitors that block the active site and enhance p38α dephosphorylation by stabilizing an accessible activation loop conformation.

Allosteric regulation of the tyrosine phosphatase PTP1B by a protein-protein interaction

This paper shows that Grb2 binding to PTP1B allosterically enhances its catalytic activity through structural changes, revealing a new regulatory mechanism for PTP1B in cell signaling.

Rigosertib reverses hypertrophic cardiomyopathy in RAF1-associated Noonan syndrome

This paper shows rigosertib reverses hypertrophic cardiomyopathy in RAF1-associated Noonan syndrome using Drosophila, iPSC, and mouse models.