A5005973308- Protein Tyrosine Phosphatases
- Galectins and Cancer Biology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Alkaline Phosphatase Research Studies
- Protein Kinase Regulation and GTPase Signaling
- RNA modifications and cancer
- PI3K/AKT/mTOR signaling in cancer
- Glycosylation and Glycoproteins Research
- Microtubule and mitosis dynamics
- Redox biology and oxidative stress
- Cytokine Signaling Pathways and Interactions
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Muscle Physiology and Disorders
- Endoplasmic Reticulum Stress and Disease
- Genetics, Aging, and Longevity in Model Organisms
- Bioactive Compounds and Antitumor Agents
- Wnt/β-catenin signaling in development and cancer
- Adipose Tissue and Metabolism
- Macrophage Migration Inhibitory Factor
- Pancreatic function and diabetes
- Melanoma and MAPK Pathways
- ATP Synthase and ATPases Research
- Mitochondrial Function and Pathology
- Liver physiology and pathology
Cold Spring Harbor Laboratory
2015-2024
New York Proton Center
2015
FC Barcelona
2013
EM Strasbourg Business School
2013
John Wiley & Sons (United Kingdom)
2013
University of Oxford
1982-2012
Stony Brook University
1998-2012
Jewish General Hospital
2008
University of Ottawa
2008
Karolinska Institutet
2008
Since their discovery, protein tyrosine phosphatases have been speculated to play a role in tumor suppression because of ability antagonize the growth-promoting kinases. Recently, suppressor from human chromosome 10q23, called PTEN or MMAC1, has identified that shares homology with phosphatase family. Germ-line mutations give rise several related neoplastic disorders, including Cowden disease. A key step understanding function as is identify its physiological substrates. Here we report...
Protein tyrosine phosphatases (PTPs) have long been thought to play a role in tumor suppression due their ability antagonize the growth promoting protein kinases. Recently, candidate suppressor from 10q23, termed P-TEN, was isolated, and sequence homology demonstrated with members of PTP family, as well cytoskeletal tensin. Here we show that recombinant P-TEN dephosphorylated peptide substrates phosphorylated on serine, threonine, residues, indicating is dual-specificity phosphatase. In...
The identification of substrates protein tyrosine phosphatases (PTPs) is an essential step toward a complete understanding the physiological function members this enzyme family. PTPs are defined by conserved catalytic domain harboring 27 invariant residues. From mutagenesis study these residues that was guided our knowledge crystal structure PTP1B, we have discovered mutation acid (Asp-181 in PTP1B) converts extremely active into “substrate trap.” Expression D181A mutant PTP1B COS and 293...
Protein tyrosine phosphatases (PTPs) constitute a family of receptor-like and cytoplasmic signal transducing enzymes that catalyze the dephosphorylation phosphotyrosine residues are characterized by homologous catalytic domains. The crystal structure representative member this family, 37-kilodalton form (residues 1 to 321) PTP1B, has been determined at 2.8 A resolution. enzyme consists single domain with site located base shallow cleft. phosphate recognition is created from loop...
Phospholipase C-gamma 1 (PLC-gamma 1), an isozyme of the phosphoinositide-specific phospholipase C family, which occupies a central role in hormonal signal transduction pathways, is excellent substrate for epidermal growth factor (EGF) receptor tyrosine kinase. Epidermal elicits phosphorylation PLC-gamma and phosphatidylinositol 4,5-bisphosphate hydrolysis various cell lines. The ability to activate catalytic activity was tested. Tyrosine intact cells or vitro increased 1. Also, treatment...
The crystal structures of a cysteine-215→serine mutant protein tyrosine phosphatase 1B complexed with high-affinity peptide substrates corresponding to an autophosphorylation site the epidermal growth factor receptor were determined. Peptide binding was accompanied by conformational change surface loop that created phosphotyrosine recognition pocket and induced catalytically competent form enzyme. side chain is buried within anchors substrate its site. Hydrogen bonds between main-chain atoms...
This report describes the purification of major protein-tyrosine-phosphatases from human placenta. Enzyme activity was followed with a novel artificial substrate, namely reduced, carboxamidomethylated, and maleylated lysozyme, phosphorylated on tyrosine by partially purified preparation insulin epidermal growth factor receptor kinases, also The key step in affinity chromatography column thiophosphorylated, lysozyme-Sepharose. Purification carried out separately both soluble particulate...
In the preceding article (Tonks, N. K., Diltz, C. D., and Fischer, E. H. (1988) J. Biol. Chem. 263, 6722-6730), purification of major protein-tyrosine-phosphatases from human placenta, some to apparent homogeneity, was described. This report compares characteristics these enzymes clearly identifies at least two distinct protein-tyrosine-phosphatase catalytic subunits. All were absolutely specific for phosphotyrosyl residues showed no activity on any phosphoseryl/phosphothreonyl-containing...
Epidermal growth factor stimulates the activity of several cytosolic serine/threonine protein kinases in quiescent Swiss 3T3 cells. Two these, which use myelin basic (MBP) as substrate, act kinase that they are able to activate a separate peptide vitro by mechanism involving phosphorylation. In this study, we have identified two activities from extracts epidermal factor-treated cells stimulate an ATP-dependent activation both MBP kinases, derived their inactive precursor forms untreated The...
A major protein tyrosine phosphatase (PTPase 1B) has been isolated in essentially homogeneous form from the soluble and particulate fractions of human placenta. Unexpectedly, partial amino acid sequences displayed no homology with primary structures Ser/Thr phosphatases deduced cDNA clones. However, sequence is strikingly similar to tandem C-terminal homologous domains leukocyte common antigen (CD45). 157-residue segment PTPase 1B 40% 33% identity corresponding regions cytoplasmic I II CD45....
Reversible inactivation by sulfhydration of the protein tyrosine phosphatase PTP1B activates kinase PERK to promote ER stress response.