• Several protein-tyrosine phosphatases (PTPs) have been proposed to act as negative regulators of insulin signaling. (rcsb.org)
  • Signal transduction of FMS-like tyrosine kinase 3 (FLT3) is regulated by protein-tyrosine phosphatases (PTPs). (nih.gov)
  • Despite low sequence similarity, the catalytic domain of SHP-1 shows high similarity in secondary and tertiary structures with other protein-tyrosine phosphatases (PTPs). (umassmed.edu)
  • Sequence alignment and structural analysis suggest that the residues in the WPD loop, especially the amino acid following Asp421, are critical for the movement of WPD loop on binding substrates and the specific activity of protein-tyrosine phosphatases. (umassmed.edu)
  • Activation of mitogen-activated protein kinase phosphatase-1 (MKP-1), dual-specificity protein phosphatase, set the mitogen-activated protein kinase signaling. (pp1a.com)
  • The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. (antibodies-online.com)
  • Protein phosphatase 1 (PP1) belongs to a certain class of phosphatases known as protein serine/threonine phosphatases. (wikipedia.org)
  • The glycogen‐associated form of protein phosphatase‐1 (PP‐1 G ) is a heterodimer comprising a 37‐kDa catalytic (C) subunit and a 161‐kDa glycogen‐binding (G) subunit, the latter being phosphorylated by cAMP‐dependent protein kinase at two serine residues (site 1 and site 2). (dundee.ac.uk)
  • 4 While proteins can be phosphorylated on nine amino acids, serine, threonine and tyrosine phosphorylation are by far the most predominant in eukaryotic cells. (ac.be)
  • SIRT2 is involved in cisplatin-induced acute kidney injury through regulation of mitogen-activated protein kinase phosphatase - 1 . (pp1a.com)
  • These protein kinases correspond to alternatively spliced isoforms derived from the JNK1, JNK2 and JNK3 genes. (umassmed.edu)
  • These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. (antibodies-online.com)
  • Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. (antibodies-online.com)
  • In the past, most of the attention was focused primarily on protein kinases and on their regulation, mainly because phosphatases were then viewed as simple housekeeping enzymes. (ac.be)
  • But advances in the understanding of protein phosphatases make now clear that these enzymes are precisely regulated and are as important as kinases in the regulation of cellular processes involving protein phosphorylation. (ac.be)
  • Protein phosphatases reverse the covalent modifications of numerous cellular proteins imposed by the activation of protein kinases and, therefore, play key role in cell signaling metabolism, growth and differentiation. (bvsalud.org)
  • Regulation of HIV-1 transcription by Protein Phosphatase 1 (PP1). (wikipedia.org)
  • This study addressed the role of DEP-1 for regulation of the acute myeloid leukemia (AML)-related mutant FLT3 internal tandem duplication (ITD) protein. (nih.gov)
  • Regulation of protein phosphatase‐1G from rabbit/skeletal muscle: 1. (dundee.ac.uk)
  • The AAA-ATPase (ATPases associated with diverse cellular activities) valosin-containing protein (VCP), is essential for many cellular pathways including but not limited to endoplasmic reticulum-associated degradation (ERAD), DNA damage responses, and cell cycle regulation. (portlandpress.com)
  • Due to its abundance and versatile function, VCP participates in many cellular pathways including ERAD, endolysosomal trafficking, selective autophagy, cell cycle regulation, and DNA damage signaling [ 1 ]. (portlandpress.com)
  • Although intracellular signal transduction is often portrayed as a protein kinase 'domino effect', the counterbalancing function of phosphatases, and thus the control of phosphatase activity, is equally relevant to proper regulation of cellular function. (ac.be)
  • Regulation of protein phosphorylation in β-cells has been extensively investigated, but less is known about protein dephosphorylation. (lu.se)
  • 1 Reversible protein phosphorylation is an important regulatory mechanism that controls the activities of a myriad of proteins and is thus involved in virtually every major physiological process. (ac.be)
  • The cdc25 gene product is a tyrosine phosphatase that acts as an initiator of M-phase in eukaryotic cell cycles by activating p34 cdc2 . (biologists.com)
  • The crystal structures of the protein-tyrosine phosphatase SHP-1 catalytic domain and the complex it forms with the substrate analogue tungstate have been determined and refined to crystallographic R values of 0.209 at 2.5 A resolution and 0.207 at 2.8 A resolution, respectively. (umassmed.edu)
  • In contrast to the conformational changes observed in the crystal structures of PTP1B and Yersinia PTP, the WPD loop (Trp419-Pro428) in the catalytic domain of SHP-1 moves away from the substrate binding pocket after binding the tungstate ion. (umassmed.edu)
  • Site 2 was a good substrate for all three type‐2 phosphatases (2A, 2B and 2C) with t 0.5 values less than those toward the α subunit of phosphorylase kinase. (dundee.ac.uk)
  • Site 1 was at least 10‐fold less effective than site 2 as a substrate for all four phosphatases. (dundee.ac.uk)
  • Desensitization of p21(ras) after stimulation of cells by growth factors and phorbol 12-myristate 13-acetate (PMA) correlates with hyperphosphorylation of the guanine nucleotide exchange factor Son-of-sevenless (Sos) and its dissociation from the adaptor protein Grb2 (Cherniack, A., Klarlund, J. K., Conway, B. R., and Czech, M. P. (1995) J. Biol. (umassmed.edu)
  • Receptor dimerization and autophosphorylation attracts proteins containing Src homology 2 (SH2) or phosphotyrosine binding (PTB) domains including adaptor proteins like FRS2 and GRB2. (springer.com)
  • VCP identifies ubiquitylated substrates through numerous dedicated adaptor proteins and unfolds substrates by threading them through a central pore in the hexamer ( Figure 1 ). (portlandpress.com)
  • VCP interacts with adaptor proteins to identify ubiquitylated substrates for degradation by the proteasome. (portlandpress.com)
  • Protein phosphatase 2A (PP2A) regulate critical cell signaling and the human tumor suppressor. (pp1a.com)
  • Both Northern and Western blot analyses confirmed the increased expression of one of the cDNA species identified as coding for the catalytic subunit of protein phosphatase 2A (PP2A), an observation not previously reported during the response to a growth factor. (edu.au)
  • To determine the significance of the increased expression of PP2A in response to CSF-1, the PP2A inhibitor okadaic acid (OA) was added to CSF-1-treated BMM and found to inhibit DNA synthesis in a dose-dependent manner. (edu.au)
  • Further analysis with flow cytometry in the presence of OA led to the novel conclusion that PP2A activity is critical for CSF-1-driven BMM cell cycle progression in both early G1 and S phases. (edu.au)
  • Surprisingly, in the light of previous studies with other cells, the PP2A-dependent proliferation could be dissociated from activation by extracellular signal-regulated protein kinase (ERK) in macrophages because OA did not affect either the basal or CSF-1-induced ERK activity in BMM. (edu.au)
  • Two-dimensional SDS/PAGE analysis of lysates of 32P-labelled BMM, which had been treated with CSF-1 in the presence or absence of OA, identified candidate substrates for PP2A. (edu.au)
  • Nouvelles avancées dans la structure et la régulation de la Protéine Phosphatase 2A : les raisons pour lesquelles PP2A ne doit plus être considérée comme une enzyme passive et non spécifique. (ac.be)
  • La Protéine Phosphatase 2A (PP2A) est une phosphatase très abondante composée d'un noyau dimérique contenant une sous-unité catalytique (C) et une sous-unité structurale (A), auquel est associé une sous-unité régulatrice (B) variable. (ac.be)
  • Bien que considérée dans le passé comme une enzyme constitutive non spécifique, PP2A est une phosphatase soumise à une régulation précise et qui est importante dans le contrôle des fonctions cellulaires impliquant la phosphorylation. (ac.be)
  • Protein Phosphatase 2A (PP2A) is a widely expressed family of protein phosphatases made of a core dimer, composed of a catalytic (C) subunit and a structural (A) subunit, in association with a third variable regulatory (B) subunit. (ac.be)
  • Although viewed as a constitutive housekeeping enzyme in the past, PP2A is a highly regulated phosphatase and is emerging as an important regulator of multiple cellular processes involving protein phosphorylation. (ac.be)
  • 2 Protein phosphatase 2A (PP2A) is a very abundant - it accounts for as much as 1% of total cellular proteins - ubiquitous and remarkably conserved enzyme. (ac.be)
  • Release of C subunit was also induced by the binding of anti‐site‐1 Fab fragments to glycogen‐bound PP‐1 G . At near physiological ionic strength, PP‐1 G and glycogen concentration, site 2 was autodephosphorylated by PP‐1 G with a t 0.5 of 2.6 min at 30°C, ∼ 100‐fold slower than the t 0.5 for dephosphorylation of glycogen phosphorylase under the same conditions. (dundee.ac.uk)
  • The efficient dephosphorylation of site 2 by the Ca 2+ /calmodulin‐stimulated protein phosphatase (2B) provides a potential mechanism for regulating PP‐1 activity in response to Ca 2+ , and represents an example of a protein phosphatase cascade. (dundee.ac.uk)
  • To understand the role of protein dephosphorylation in β-cells and type 2 diabetes (T2D), we first examined mRNA expression of the type 2C family (PP2C) of protein phosphatases in islets from T2D donors. (lu.se)
  • Structure-based design, guided by PTP mutants and x-ray protein crystallography, was used to optimize a relatively weak, nonphosphorus, nonpeptide general PTP inhibitor (2-(oxalyl-amino)-benzoic acid) into a highly selective PTP1B inhibitor. (rcsb.org)
  • Phosphoproteome and drug response effects mediated by the three Protein Phosphatase 2A inhibitor proteins CIP2A, SET and PME- 1 . (pp1a.com)
  • Using Ptpn22 −/− mice we demonstrate that the phosphatase PTPN22 is a highly selective, negative regulator of cDC2 homeostasis, preventing excessive population expansion from as early as 3 weeks of age. (frontiersin.org)
  • Valosin-containing protein (VCP, also p97, or Cdc48p in yeast) is an evolutionarily conserved, homo-hexameric, ubiquitin-selective, AAA-ATPase that functions in numerous ubiquitin-dependent protein quality control pathways. (portlandpress.com)
  • In conjunction with information presented in the following paper in this issue of this journal, the results substantiate the hypothesis that PP‐1 activity towards the glycogen‐metabolising enzymes is regulated in vivo by reversible phosphorylation of a targetting subunit (G) that directs the C subunit to glycogen-protein particles. (dundee.ac.uk)
  • The protein kinase activity of these JNK isoforms was measured using the transcription factors ATF2, Elk-1 and members of the Jun family as substrates. (umassmed.edu)
  • This suggests that dysfunctional phosphatases play a role in Alzheimer's disease. (wikipedia.org)
  • Our experiments revealed that DEP-1 was expressed but dysfunctional in cells transformed by FLT3 ITD. (nih.gov)
  • It has been recognized that protein phosphatase-1 (PP1) serves as an important regulator of HIV-1 transcription. (wikipedia.org)
  • We recently identified the PTP DEP-1/CD148/PTPRJ as a novel negative regulator of FLT3. (nih.gov)
  • A subclass of receptor-like protein tryosine phosphatases that contain a single cytosolic protein tyrosine phosphate domain and multiple extracellular fibronectin III-like domains. (online-medical-dictionary.org)
  • In TGF-beta-treated MCF10A mammary epithelial cells overexpressing HER2 and by chromatin immunoprecipitation, we identified novel Smad targets including protein tyrosine phosphatase receptor type kappa (PTPRK). (nih.gov)
  • protein tyrosine phosphatase, non-receptor. (wikigenes.org)
  • The receptor for CSF-1 is the product of the c-fms proto-oncogene, which, on binding ligand, can stimulate a mitogenic response in the appropriate cells. (edu.au)
  • Endocytic trafficking dynamically regulates neuronal plasma membrane protein presentation and activity, and plays a central role in excitability and plasticity. (umassmed.edu)
  • Over the course of my dissertation research I investigated endocytic mechanisms regulating two neuronal membrane proteins: the anesthetic-activated potassium leak channel, KCNK3, as well as the psychostimulant-sensitive dopamine transporter (DAT). (umassmed.edu)
  • Taken together, these results demonstrate that novel, non-classical endocytic mechanisms dynamically control the plasma membrane presentation of these two important neuronal proteins. (umassmed.edu)
  • Among them are the Sprouty proteins which mainly act as inhibitors of growth factor-dependent neuronal and glial signaling pathways. (springer.com)
  • On the contrary, knockdown of Sprouty proteins increases proliferation of activated astrocytes and, consequently, reduces secondary brain damage in neuronal lesion models such as kainic acid-induced epilepsy or endothelin-induced ischemia. (springer.com)
  • They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. (antibodies-online.com)
  • Protein crowding induces membrane curvatures through an entropic mechanism. (portlandpress.com)
  • Crowding of asymmetric proteins results in an asymmetric lateral pressure across the membrane which can be used by cells in a number of biological processes involving membrane remodeling. (portlandpress.com)
  • To investigate which genes are regulated in response to CSF-1-stimulation in murine bone-marrow-derived macrophages (BMM), we employed mRNA differential display reverse transcriptase-mediated PCR to identify cDNA species induced by CSF-1. (edu.au)
  • The protein composition of saliva also reflects cellular signal processing that results from day-to-day environmental influences, as well as from acute or chronic stress 9 . (bvsalud.org)
  • My results indicate that KCNK3 internalizes in response to Protein Kinase C (PKC) activation, using a novel pathway that requires the phosphoserine binding protein, 14-3-3β, and demonstrates for the first time regulated KCNK3 channel trafficking in neurons. (umassmed.edu)
  • Treatment of cells with interleukin-1 (IL-1) caused activation of the JNK isoforms. (umassmed.edu)
  • This activation was blocked by expression of the MAP kinase phosphatase MKP-1. (umassmed.edu)
  • Colony-stimulating factor 1 (CSF-1) is required for the development of monocytes/macrophages from progenitor cells and for the survival and activation of mature macrophages. (edu.au)
  • In Alzheimer's, hyperphosphorylation of the microtubule-associated protein inhibits the assembly of microtubules in neurons. (wikipedia.org)
  • This binding to phosphorylase a prevents any phosphatase activity of PP1 and maintains the glycogen phosphorylase in its active phosphorylated configuration. (wikipedia.org)
  • Protein kinase A can reduce the activity of PP1. (wikipedia.org)
  • Researchers at the New York State Institute for Basic Research in Developmental Disabilities showed that there is significantly lower type 1 phosphatase activity in both gray and white matters in Alzheimer disease brains. (wikipedia.org)
  • Comparison of the binding activity of the JNK isoforms demonstrated that the JNK proteins differ in their interaction with ATF2, Elk-1 and Jun transcription factors. (umassmed.edu)
  • At physiological ionic strength, phosphorylation of glycogen‐bound PP‐1 G was found to release all the phosphatase activity from glycogen. (dundee.ac.uk)
  • The released activity was free C subunit, and not PP‐1 G , while the phospho‐G subunit remained bound to glycogen. (dundee.ac.uk)
  • In mice, cDCs (CD11c + MHCII + ) are sub-divided into functionally distinct phenotypes defined as cDC1 (CD8 + IRF8 + XCR1 + Clec9a + CD24 + ) and cDC2 (IRF4 + CD11b + SIRPα + ) whilst in humans the equivalent DC subsets are defined by expression of CD8 + IRF8 + XCR1 + Clec9a + CD141 + (cDC1) and IRF4 + CD1c + (cDC2) ( 1 - 4 ). (frontiersin.org)
  • RTK-dependent signaling pathways provide a variety of targets for the treatment of neurological and neuropsychiatric disorders in which neurotrophins and other growth factors are released [ 8 , 9 ] (Fig. 1 ). (springer.com)
  • VCP primarily identifies ubiquitylated proteins in these pathways and mediates their unfolding and degradation by the 26S proteasome. (portlandpress.com)
  • At the levels present in skeletal muscle, the type‐2A and type‐2B phosphatases are potentially capable of dephosphorylating site 2 in vivo within seconds. (dundee.ac.uk)
  • This type of phosphatase includes metal-dependent protein phosphatases (PPMs) and aspartate-based phosphatases. (wikipedia.org)
  • In intact cells, including primary AML cells, FLT3 ITD kinase inhibition reactivated DEP-1. (nih.gov)
  • DEP-1 reactivation was also achieved by counteracting the high levels of reactive oxygen species (ROS) production detected in FLT3 ITD-expressing cell lines by inhibition of reduced NAD phosphate (NADPH)-oxidases, or by overexpression of catalase or peroxiredoxin-1 (Prx-1). (nih.gov)
  • Interference with ROS production in 32D cells inhibited cell transformation by FLT3 ITD in a DEP-1-dependent manner, because RNAi-mediated depletion of DEP-1 partially abrogated the inhibitory effect of ROS quenching. (nih.gov)
  • This was caused by enzymatic inactivation of DEP-1 through oxidation of the DEP-1 catalytic cysteine. (nih.gov)
  • Since the protein lacks enzymatic activities, it will be difficult to develop chemical compounds capable to directly and specifically modulate Sprouty functions. (springer.com)
  • Dendritic cells (DCs) are specialized antigen presenting cells that sense danger signals and instruct T cell responses ( 1 ). (frontiersin.org)
  • Functionally, cDC1 cross-present exogenous antigens to activate CD8 + T cells and can promote IL-12 dependent Th1 responses ( 1 , 5 - 7 ). (frontiersin.org)
  • Silencing of PPM1E increased glucose-stimulated insulin secretion (GSIS) in INS-1 832/13 cells and/or islets from patients with T2D, whereas PPM1E overexpression decreased. (lu.se)
  • Reactivation of DEP-1 by stable overexpression of Prx-1 extended survival of mice in the 32D cell/C3H/HeJ mouse model of FLT3 ITD-driven myeloproliferative disease. (nih.gov)
  • Phosphatase expression overall was changed in T2D, and that of PPM1E was the most markedly downregulated. (lu.se)
  • The catalytic subunit consists of a 30-kD single-domain protein that can form complexes with other regulatory subunits. (wikipedia.org)