Protein Tyrosine Phosphatases

Phosphoproteome-derived peptide libraries for deep specificity profiling of phosphatases and phospholyases

The paper develops a method to profile phosphatase and phospholyase specificity using phosphoproteome-derived peptide libraries and mass spectrometry, revealing sequence preferences and enzyme selectivity.

PTPN22 Regulates T Cell Synapse Formation through PSTPIP1-Dependent Actin Remodeling

This study shows PTPN22 regulates actin remodeling via PSTPIP-1 during T cell synapse formation, affecting TCR clustering and activation.

Multiplexed single-cell transcriptomics reveals diverse phenotypic outcomes for pathogenic SHP2 variants

This study uses single-cell transcriptomics to analyze how diverse SHP2 variants affect gene expression and cellular phenotypes in relation to disease.

Ganaxolone, an approved therapy for CDKL5-Deficiency Disorder, is an inhibitor of PTP1B

This study shows that Ganaxolone inhibits PTP1B, restores TRKB/BDNF signaling, and rescues cellular morphology in CDKL5-deficient cells.

Blocking SHP2 benefits FGFR2 inhibitor and overcomes its resistance in FGFR2-amplified gastric cancer

This paper shows that blocking SHP2 enhances FGFR2 inhibitor effectiveness and overcomes resistance in FGFR2-amplified gastric cancer by inhibiting feedback pathways and boosting T cell immunity.

A druggable redox switch on SHP1 controls macrophage inflammation

This paper identifies a druggable redox switch on SHP1 that controls macrophage inflammation by developing a covalent agonist targeting a specific cysteine residue.

A CDCA2 - MYC positive feedback loop controls cancer cells survival

The paper identifies a CDCA2-MYC positive feedback loop that promotes cancer cell survival in multiple cancer types.

A Hotspot Phosphorylation Site on SHP2 Drives Oncoprotein Activation and Drug Resistance

This paper identifies phosphorylation of SHP2 at tyrosine 62 as a mechanism of resistance to SHP2 inhibitors and a new drug target.

Pervanadate-induced oxidation relieves autoinhibition of SRC protein tyrosine kinase

This paper shows that pervanadate induces oxidation, which activates SRC kinases by disrupting autoinhibition and altering SH2 domain phosphopeptide binding, revealing a redox-dependent mechanism for SRC activation.

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.

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.

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.

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.

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.

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.

Reversible control of kinase signaling through chemical-induced dephosphorylation

This study uses an ABA-induced proximity system to reversibly control kinase signaling by recruiting phosphatases, revealing how phosphatases regulate oncogenic kinases like BCR::ABL1, BRAF(V600E), and MEK1.