A5085618254- Protein Tyrosine Phosphatases
- Galectins and Cancer Biology
- RNA modifications and cancer
- Cytokine Signaling Pathways and Interactions
- Acute Myeloid Leukemia Research
- ATP Synthase and ATPases Research
- Cancer, Hypoxia, and Metabolism
- Hematopoietic Stem Cell Transplantation
- Mitochondrial Function and Pathology
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- Adipose Tissue and Metabolism
- Ubiquitin and proteasome pathways
- PI3K/AKT/mTOR signaling in cancer
- High Altitude and Hypoxia
- Pluripotent Stem Cells Research
- Metabolism, Diabetes, and Cancer
- Cardiomyopathy and Myosin Studies
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Metabolism and Genetic Disorders
- Cancer-related Molecular Pathways
- Autophagy in Disease and Therapy
- Liver physiology and pathology
- Cell Adhesion Molecules Research
Children's Healthcare of Atlanta
2016-2025
Aflac (United States)
2016-2025
Emory University
2015-2024
Shenyang University of Technology
2024
University of Cambridge
2024
Stem Cell Institute
2024
Medical Research Council
2024
Wellcome Trust
2024
Case Western Reserve University
2010-2023
Winship Cancer Institute
2019-2023
Shp-2, a widely expressed cytoplasmic tyrosine phosphatase with two SH2 domains, is believed to participate in signal relay downstream of growth factor receptors. We show here that this also plays an important role the control cell spreading, migration, and cytoskeletal architecture. Fibroblast cells lacking functional Shp-2 were impaired their ability spread migrate on fibronectin compared wild-type cells. Furthermore, mutant displayed increased number focal adhesions condensed F-actin...
Coagulation factor XII (FXII) deficiency is associated with decreased neutrophil migration, but the mechanisms remain uncharacterized. Here, we examine how FXII contributes to inflammatory response. In 2 models of sterile inflammation, FXII-deficient mice (F12-/-) had fewer neutrophils recruited than WT mice. We discovered that produced a pool functionally distinct from hepatic-derived and trafficking at sites inflammation. signals in through urokinase plasminogen activator receptor-mediated...
AbstractShp-1 and Shp-2 are cytoplasmic protein tyrosine phosphatases that contain two Src homology 2 (SH2) domains. A negative regulatory role of Shp-1 in hematopoiesis has been strongly implicated by the phenotype motheaten mice with a mutation locus, which is characterized leukocyte hypersensitivity, deregulated mast cell function, excessive erythropoiesis. targeted deletion 65 amino acids N-terminal SH2 (SH2-N) domain leads to an embryonic lethality at midgestation homozygous mutant...
Activating mutations in protein tyrosine phosphatase 11 (Ptpn11) have been identified childhood acute leukemias, addition to juvenile myelomonocytic leukemia (JMML), which is a myeloproliferative disorder (MPD). It not clear whether activating of this play causal role the pathogenesis leukemias. If so, cell origin leukemia-initiating stem cells (LSCs) remains be determined. Ptpn11(E76K) mutation most common and active Ptpn11 found JMML However, pathogenic effects well characterized. We...
Abstract Mutations that decrease or increase the activity of tyrosine phosphatase, SHP2 (encoded by PTPN11 ), promotes developmental disorders and several malignancies varying phosphatase activity. We uncovered is a distinct class an epigenetic enzyme; upon phosphorylation kinase ACK1/TNK2, pSHP2 was escorted androgen receptor (AR) to chromatin, erasing hitherto unidentified pY54-H3 (phosphorylation histones H3 at Tyr54) marks trigger transcriptional program AR. Noonan Syndrome with Multiple...
Shp-2 is a cytoplasmic tyrosine phosphatase that contains two Src homology 2 (SH2) domains at the N terminus.Biochemical data suggests acts downstream of variety receptor and kinases.A targeted deletion mutation in N-terminal SH2 (SH2-N) domain results embryonic lethality homozygous mutant mice midgestation.In vitro stem (ES) cell differentiation assays suggest might play an important role hematopoiesis.By aggregating (Shp-2 ؊/؊ ) ES cells wild-type (WT) embryos, we created -WT chimeric...
By using both genetic and biochemical approaches, we have investigated the physiological role of Shp-2, a cytoplasmic tyrosine phosphatase with two Src homology 2 domains, in signaling pathways downstream epidermal growth factor receptor (EGF-R). In previous studies, targeted deletion mutation SH2-N domain Shp-2 was introduced into murine locus, which resulted embryonic lethality homozygous mutant ( −/− ) mice at midgestation. aggregating stem cells wild-type embryos, created /wild-type...
Activating mutations of PTPN11 (encoding the SHP2 phosphatase) are associated with Noonan syndrome, childhood leukemias, and sporadic solid tumors. Virtual screening combined experimental assays was performed to identify inhibitors from a database natural products. This effort led identification cryptotanshinone as an inhibitor SHP2. Cryptotanshinone inhibited IC50 22.50 μM. Fluorescence titration experiments confirmed that it directly bound Enzymatic kinetic analyses showed mixed-type...
Copious expression of protein arginine methyltransferase 1 (PRMT1) is associated with poor survival in many types cancers, including acute myeloid leukemia. We observed that a specific megakaryocytic leukemia (AMKL) cell line (6133) derived from RBM15-MKL1 knock-in mice exhibited heterogeneity Prmt1 levels. Interestingly, only subpopulation 6133 cells expressing high levels caused when transplanted into congenic mice. The PRMT1 inhibitor, MS023, effectively cured this PRMT1-driven Seahorse...
Copious expression of protein arginine methyltransferase 1 (PRMT1) is associated with poor survival in many types cancers, including acute myeloid leukemia. We observed that a specific megakaryocytic leukemia (AMKL) cell line (6133) derived from RBM15-MKL1 knock-in mice exhibited heterogeneity Prmt1 levels. Interestingly, only subpopulation 6133 cells expressing high levels caused when transplanted into congenic mice. The PRMT1 inhibitor, MS023, effectively cured this PRMT1-driven Seahorse...
Chemokines regulate a number of biological processes, including trafficking diverse leukocytes and proliferation myeloid progenitor cells. SHP-1 (Src homology 2 domain tyrosine phosphatase 1), phosphotyrosine phosphatase, is considered an important regulator signaling for cytokine receptors. Since specific phosphorylation proteins activities induced by chemokines, we examined the role in functions chemokines using viable motheaten (mev/mev) mice that were deficient SHP-1. Chemotactic...