The Experts below are selected from a list of 225 Experts worldwide ranked by ideXlab platform

Christina Anne Mitchell - One of the best experts on this subject based on the ideXlab platform.

  • Regulation of PtdIns(3,4,5)P3/Akt signalling by inositol polyphosphate 5-Phosphatases.
    Biochemical Society Transactions, 2016
    Co-Authors: Matthew Eramo, Christina Anne Mitchell
    Abstract:

    The phosphoinositide 3-kinase (PI3K) generated lipid signals, PtdIns(3,4,5) P 3 and PtdIns(3,4) P 2, are both required for the maximal activation of the serine/threonine kinase proto-oncogene Akt. The inositol polyphosphate 5-Phosphatases (5-Phosphatases) hydrolyse the 5-position phosphate from the inositol head group of PtdIns(3,4,5) P 3 to yield PtdIns(3,4) P 2. Extensive work has revealed several 5-Phosphatases inhibit PI3K-driven Akt signalling, by decreasing PtdIns(3,4,5) P 3 despite increasing cellular levels of PtdIns(3,4) P 2. The roles that 5-Phosphatases play in suppressing cell proliferation and transformation are slow to emerge; however, the 5-Phosphatase PIPP [proline-rich inositol polyphosphate 5-Phosphatase; inositol polyphosphate 5-Phosphatase ( INPP5J )] has recently been identified as a putative tumour suppressor in melanoma and breast cancer and SHIP1 [SH2 (Src homology 2)-containing inositol Phosphatase 1] inhibits haematopoietic cell proliferation. INPP5E regulates cilia stability and INPP5E mutations have been implicated ciliopathy syndromes. This review will examine 5-Phosphatase regulation of PI3K/Akt signalling, focussing on the role PtdIns(3,4,5) P 3 5-Phosphatases play in developmental diseases and cancer. * 3AC, : 3-a-aminocholestane; 5-Phosphatases, : inositol polyphosphate 5-Phosphatases; AURKA, : aurora kinase A; BJAB, : human B-cell lymphoma cell line; BMMC, : bone marrow-derived mast cells; CHO, : Chinese hamster ovary; EGF, : epidermal growth factor; ENU, : N -ethyl- N -nitrosourea; ER, : estrogen receptor; FoxO, : forkhead box, class O; GLUT4, : glucose transporter type 4; Gpr161, : G-protein-coupled receptor 161; HEK, : human embryonic kidney; IGF-1, : insulin-like growth factor-1; IL-3, : interleukin-3; LPS, : lipopolysaccharide; MEF, : mouse embryonic fibroblast; MM, : multiple myeloma; mTORC, : mammalian target of rapamycin complex; NFAT, : nuclear factor of activated T cells; OCRL, : oculocerebrorenal syndrome of Lowe; Pak1, : P21-activated kinase 1; PDK1, : phosphoinositide-dependent kinase 1; PH, : pleckstrin homology; 1PIE, : (2-phenyl-benzo[ h ]quinolin-4-yl)-[2]piperidyl-methanol hydrochloride; 2PIQ, : 1-[(chlorophenyl)methyl]-2-methyl-5-(methylthio)-1H-indole-3-ethanamine hydrochloride; 6PTQ, : (2-adamantan-1-yl-6,8-dichloro-quinolin-4-yl)-pyridin-2-yl-methanol hydrochloride; PI3K, : phosphoinositide 3-kinase; PIPP, : proline-rich inositol polyphosphate 5-Phosphatase; PRAS40, : proline-rich Akt substrate of 40 kDa; PTEN, : Phosphatase and tensin homologue deleted on chromosome 10; PyMT, : polyoma middle T; Rheb, : Ras homologue enriched in brain; RhoGAP, : Rho GTP-ase activating protein; SAG, : smoothened agonist; Shh, : sonic hedgehog; SHIP, : SH2-containing inositol Phosphatase; SKICH, : SKIP carboxy homology; SKIP, : skeletal muscle- and kidney-enriched inositol Phosphatase; TNFα, : tumour necrosis factor α; TSC, : tuberous sclerosis; TULP3, : Tubby-like protein 3

  • Mammalian inositol polyphosphate 5-Phosphatase II can compensate for the absence of all three yeast Sac1-like-domain-containing 5-Phosphatases.
    Biochemical Journal, 2001
    Co-Authors: Cindy J. O’malley, Anne Mandy Kong, Brad K Mccoll, Joseph F. Sambrook, Sarah Ellis, P P W Wijayaratnam, Christina Anne Mitchell
    Abstract:

    Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5) P 2 ] plays a complex role in generating intracellular signalling molecules, and also in regulating actin-binding proteins, vesicular trafficking and vacuolar fusion. Four inositol polyphosphate 5-Phosphatases (hereafter called 5-Phosphatases) have been identified in Saccharomyces cerevisiae : Inp51p, Inp52p, Inp53p and Inp54p. Each enzyme contains a 5-Phosphatase domain which hydrolyses PtdIns(4,5) P 2 , forming PtdIns4 P , while Inp52p and Inp53p also express a polyphosphoinositide Phosphatase domain within the Sac1-like domain. Disruption of any two yeast 5-Phosphatases containing a Sac1-like domain results in abnormalities in actin polymerization, plasma membrane, vacuolar morphology and bud-site selection. Triple null mutant 5-Phosphatase strains are non-viable. To investigate the role of PtdIns(4,5) P 2 in mediating the phenotype of double and triple 5-Phosphatase null mutant yeast, we determined whether a mammalian PtdIns(4,5) P 2 5-Phosphatase, 5-Phosphatase II, which lacks polyphosphoinositide Phosphatase activity, could correct the phenotype of triple 5-Phosphatase null mutant yeast and restore cellular PtdIns(4,5) P 2 levels to near basal values. Mammalian 5-Phosphatase II expressed under an inducible promoter corrected the growth, cell wall, vacuolar and actin polymerization defects of the triple 5-Phosphatase null mutant yeast strains. Cellular PtdIns(4,5) P 2 levels in various 5-Phosphatase double null mutant strains demonstrated significant accumulation (4.5-, 3- and 2-fold for ∆ inp51 ∆ inp53 , ∆ inp51 ∆ inp52 and ∆ inp52 ∆ inp53 double null mutants respectively), which was corrected significantly following 5-Phosphatase II expression. Collectively, these studies demonstrate the functional and cellular consequences of PtdIns(4,5) P 2 accumulation and the evolutionary conservation of function between mammalian and yeast PtdIns(4,5) P 2 5-Phosphatases.

  • The Inositol Polyphosphate 5-Phosphatases and the Apurinic/Apyrimidinic Base Excision Repair Endonucleases Share a Common Mechanism for Catalysis
    Journal of Biological Chemistry, 2000
    Co-Authors: James C. Whisstock, Susana Romero, Rajendra Gurung, Harshal Hanumant Nandurkar, Lisa M Ooms, Stephen P. Bottomley, Christina Anne Mitchell
    Abstract:

    Abstract Inositol polyphosphate 5-Phosphatases (5-Phosphatase) hydrolyze the 5-position phosphate from the inositol ring of phosphatidylinositol-derived signaling molecules; however, the mechanism of catalysis is only partially characterized. These enzymes play critical roles in regulating cell growth, apoptosis, intracellular calcium oscillations, and post-synaptic vesicular trafficking. The UCLA fold recognition server (threader) predicted that the conserved 300-amino acid catalytic domain, common to all 5-Phosphatases, adopts the fold of the apurinic/apyrimidinic (AP) base excision repair endonucleases. PSI-BLAST searches of GENPEPT, using the amino acid sequence of AP endonuclease exonuclease III, identified all members of the 5-Phosphatase family with highly significant scores. A sequence alignment between exonuclease III and all known 5-Phosphatases revealed six highly conserved motifs containing residues that corresponded to the catalytic residues in the AP endonucleases. Mutation of each of these residues to alanine in the mammalian 43-kDa, or yeast Inp52p 5-Phosphatase, resulted in complete loss of enzyme activity. We predict the 5-Phosphatase enzymes share a similar mechanism of catalysis to the AP endonucleases, consistent with other common functional similarities such as an absolute requirement for magnesium for activity. Based on this analysis, functional roles have been assigned to conserved residues in all 5-Phosphatase enzymes.

Mitsuo Ikebe - One of the best experts on this subject based on the ideXlab platform.

  • Correlation between high temperature dependence of smooth muscle myosin light chain Phosphatase activity and muscle relaxation rate.
    The Journal of biological chemistry, 1994
    Co-Authors: Toshiaki Mitsui, Toshio Kitazawa, Mitsuo Ikebe
    Abstract:

    Abstract Q10 values of the protein Phosphatases that can dephosphorylate the regulatory light chain of smooth muscle myosin were determined. Six Phosphatases were examined, i.e. skeletal muscle protein Phosphatase 1c; protein Phosphatase 2Ac; smooth muscle Phosphatases (SMP) I, II, and IV; and myosin-associated protein Phosphatase (MAP Phosphatase). Among them, SMP-IV and MAP Phosphatase, which can dephosphorylate intact smooth muscle myosin, showed extremely high Q10 values (5.3 and 5.2, respectively). On the other hand, the Q10 values of other tested Phosphatases were within the range of the normal enzyme reaction (Q10 = 2.0). The rate of dephosphorylation of the myosin light chain in alpha-toxin-skinned strips was measured at different temperatures. The results provided a Q10 of 5.1, which was quite similar to those values obtained for SMP-IV and MAP Phosphatase. These results suggest that the physiological myosin light chain Phosphatases are SMP-IV and/or MAP Phosphatase, i.e. type 1 protein Phosphatases. The temperature dependence of maximum force, the steady-state extent of myosin light chain phosphorylation, and the relaxation rate of alpha-toxin-permeabilized rabbit portal vein smooth muscle strips were measured. Both maximum force and the extent of myosin light chain phosphorylation were significantly higher at lower temperature (15 degrees C) than at higher temperature (25 degrees C) under all pCa conditions tested, i.e. > 8, 6.3, and 5. The temperature dependence of the relaxation rate was much steeper (decreased 4 times by lowering the temperature from 25 to 15 degrees C) than that of the initial rate of increase in force development (decreased 1.4 times by lowering the temperature from 25 to 15 degrees C). These results are consistent with the Q10 values of myosin light chain Phosphatases (Q10 = 5) and myosin light chain kinase (Q10 = 1.7) and further show that the smooth muscle type 1 Phosphatases are responsible for the dephosphorylation of smooth muscle myosin in situ.

Marc C. Mumby - One of the best experts on this subject based on the ideXlab platform.

  • Site-specific dephosphorylation of smooth muscle myosin light chain kinase by protein Phosphatases 1 and 2A.
    Biochemistry, 1992
    Co-Authors: Masao Nomura, James T. Stull, Kristine E. Kamm, Marc C. Mumby
    Abstract:

    Smooth muscle myosin light chain kinase is phosphorylated at two sites (A and B) by different protein kinases. Phosphorylation at site A increases the concentration of Ca2+/calmodulin required for kinase activation. Diphosphorylated myosin light chain kinase was used to determine the site-specificity of several forms of protein serine/threonine Phosphatase. These Phosphatases readily dephosphorylated myosin light chain kinase in vitro and displayed differing specificities for the two phosphorylation sites. Type 2A protein Phosphatase specifically dephosphorylated site A, and binding of Ca2+/calmodulin to the kinase had no effect on dephosphorylation. The purified catalytic subunit of type 1 protein Phosphatase dephosphorylated both sites in the absence of Ca2+/calmodulin but only dephosphorylated site A in the presence of Ca2+/calmodulin. A protein Phosphatase fraction was prepared from smooth muscle actomyosin by extraction with 80 mM MgCl2. On the basis of sensitivity to okadaic acid and inhibitor 2, this activity was composed of multiple protein Phosphatases including type 1 activity. This Phosphatase fraction dephosphorylated both sites in the absence of Ca2+/calmodulin. However, dephosphorylation of both sites A and B was completely blocked in the presence of Ca2+/calmodulin. These results indicate that two phosphorylation sites of myosin light chain kinase are dephosphorylated by multiple protein serine/threonine Phosphatases with unique catalytic specificities.

Christophe Erneux - One of the best experts on this subject based on the ideXlab platform.

  • Phosphoinositide Phosphatases in a network of signalling reactions
    Pflügers Archiv - European Journal of Physiology, 2007
    Co-Authors: Daniel Blero, Bernard Payrastre, Stéphane Schurmans, Christophe Erneux
    Abstract:

    Phosphoinositide Phosphatases dephosphorylate the three positions (D-3, 4 and 5) of the inositol ring of the poly-phosphoinositides. They belong to different families of enzymes. The PtdIns(3,4)P_2 4-Phosphatase family, the tumour suppressor Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), SAC1 domain Phosphatases and myotubularins belong to the tyrosine protein Phosphatases superfamily. They share the presence of a conserved cysteine residue in the consensus CX_5RT/S. Another family consists of the inositol polyphosphate 5-Phosphatase isoenzymes. The importance of these phosphoinositide Phosphatases in cell regulation is illustrated by multiple examples of their implications in human diseases such as Lowe syndrome, X-linked myotubular myopathy, cancer, diabetes or bacterial infection.

  • The diversity and possible functions of the inositol polyphosphate 5-Phosphatases
    Biochimica et Biophysica Acta, 1998
    Co-Authors: Christophe Erneux, Cédric Govaerts, David Communi, Xavier Pesesse
    Abstract:

    Distinct forms of inositol and phosphatidylinositol polyphosphate 5-Phosphatases selectively remove the phosphate from the 5-position of the inositol ring from both soluble and lipid substrates, i.e., inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), inositol 1,3,4, 5-tetrakisphosphate (Ins(1,3,4,5)P4), phosphatidylinositol 4, 5-bisphosphate (PtdIns(4,5)P2) or phosphatidylinositol 3,4, 5-trisphosphate (PtdIns(3,4,5)P3). In mammalian cells, this family contains a series of distinct genes and splice variants. All inositol polyphosphate 5-Phosphatases share a 5-Phosphatase domain and various protein modules probably responsible for specific cell localisation or recruitment (SH2 domain, proline-rich sequences, prenylation sites, etc.). Type I Ins(1,4,5)P3 5-Phosphatase also uses Ins(1,3,4,5)P4 but not the phosphoinositides as substrates. This enzyme is targeted to specific membranes by means of a prenylation site. Type II 5-Phosphatases can use both PtdIns(4,5)P2 and PtdIns(3,4,5)P3 as substrates. Five mammalian enzymes and multiple splice variants are known: INPP5P or inositol polyphosphate 5-Phosphatase II, OCRL (a Golgi protein implicated in the Lowe oculocerebrorenal syndrome), synaptojanin (a protein involved in the recycling of synaptic vesicles), SHIP 1 and SHIP 2 (or SH2-containing inositol 5-Phosphatases). As discussed in this review, the substrate specificity, regulatory mechanisms, subcellular localisation and tissue specificity indicate that the different 5-Phosphatase isoforms may play specific roles. As known in the dephosphorylation of tyrosine containing substrates by the tyrosine protein Phosphatases or in the metabolism of cyclic nucleotides by the cyclic nucleotide phosphodiesterases, inositol polyphosphate 5-Phosphatases directly participate in the control of second messengers in response to both activation or inhibitory cell signalling.

  • The diversity and possible functions of the inositol polyphosphate 5-Phosphatases
    Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1998
    Co-Authors: Christophe Erneux, Cédric Govaerts, David Communi, Xavier Pesesse
    Abstract:

    Distinct forms of inositol and phosphatidylinositol polyphosphate 5-Phosphatases selectively remove the phosphate from the 5-position of the inositol ring from both soluble and lipid substrates, i.e. inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), inositol 1,3,4, 5-tetrakisphosphate (Ins(1,3,4,5)P4), phosphatidylinositol 4, 5-bisphosphate (PtdIns(4,5)P2) or phosphatidylinositol 3,4, 5-trisphosphate (PtdIns(3,4,5)P3). In mammalian cells, this family contains a series of distinct genes and splice variants. All inositol polyphosphate 5-Phosphatases share a 5-Phosphatase domain and various protein modules probably responsible for specific cell localisation or recruitment (SH2 domain, proline-rich sequences, prenylation sites, etc.). Type I Ins(1,4,5)P3 5-Phosphatase also uses Ins(1,3,4,5)P4 but not the phosphoinositides as substrates. This enzyme is targeted to specific membranes by means of a prenylation site. Type II 5-Phosphatases can use both PtdIns(4,5)P2 and PtdIns(3,4,5)P3 as substrates. Five mammalian enzymes and multiple splice variants are known: INPP5P or inositol polyphosphate 5-Phosphatase II, OCRL (a Golgi protein implicated in the Lowe oculocerebrorenal syndrome), synaptojanin (a protein involved in the recycling of synaptic vesicles), SHIP 1 and SHIP 2 (or SH2-containing inositol 5-Phosphatases). As discussed in this review, the substrate specificity, regulatory mechanisms, subcellular localisation and tissue specificity indicate that the different 5-Phosphatase isoforms may play specific roles. As known in the dephosphorylation of tyrosine containing substrates by the tyrosine protein Phosphatases or in the metabolism of cyclic nucleotides by the cyclic nucleotide phosphodiesterases, inositol polyphosphate 5-Phosphatases directly participate in the control of second messengers in response to both activation or inhibitory cell signalling.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Xavier Pesesse - One of the best experts on this subject based on the ideXlab platform.

  • The diversity and possible functions of the inositol polyphosphate 5-Phosphatases
    Biochimica et Biophysica Acta, 1998
    Co-Authors: Christophe Erneux, Cédric Govaerts, David Communi, Xavier Pesesse
    Abstract:

    Distinct forms of inositol and phosphatidylinositol polyphosphate 5-Phosphatases selectively remove the phosphate from the 5-position of the inositol ring from both soluble and lipid substrates, i.e., inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), inositol 1,3,4, 5-tetrakisphosphate (Ins(1,3,4,5)P4), phosphatidylinositol 4, 5-bisphosphate (PtdIns(4,5)P2) or phosphatidylinositol 3,4, 5-trisphosphate (PtdIns(3,4,5)P3). In mammalian cells, this family contains a series of distinct genes and splice variants. All inositol polyphosphate 5-Phosphatases share a 5-Phosphatase domain and various protein modules probably responsible for specific cell localisation or recruitment (SH2 domain, proline-rich sequences, prenylation sites, etc.). Type I Ins(1,4,5)P3 5-Phosphatase also uses Ins(1,3,4,5)P4 but not the phosphoinositides as substrates. This enzyme is targeted to specific membranes by means of a prenylation site. Type II 5-Phosphatases can use both PtdIns(4,5)P2 and PtdIns(3,4,5)P3 as substrates. Five mammalian enzymes and multiple splice variants are known: INPP5P or inositol polyphosphate 5-Phosphatase II, OCRL (a Golgi protein implicated in the Lowe oculocerebrorenal syndrome), synaptojanin (a protein involved in the recycling of synaptic vesicles), SHIP 1 and SHIP 2 (or SH2-containing inositol 5-Phosphatases). As discussed in this review, the substrate specificity, regulatory mechanisms, subcellular localisation and tissue specificity indicate that the different 5-Phosphatase isoforms may play specific roles. As known in the dephosphorylation of tyrosine containing substrates by the tyrosine protein Phosphatases or in the metabolism of cyclic nucleotides by the cyclic nucleotide phosphodiesterases, inositol polyphosphate 5-Phosphatases directly participate in the control of second messengers in response to both activation or inhibitory cell signalling.

  • The diversity and possible functions of the inositol polyphosphate 5-Phosphatases
    Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1998
    Co-Authors: Christophe Erneux, Cédric Govaerts, David Communi, Xavier Pesesse
    Abstract:

    Distinct forms of inositol and phosphatidylinositol polyphosphate 5-Phosphatases selectively remove the phosphate from the 5-position of the inositol ring from both soluble and lipid substrates, i.e. inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), inositol 1,3,4, 5-tetrakisphosphate (Ins(1,3,4,5)P4), phosphatidylinositol 4, 5-bisphosphate (PtdIns(4,5)P2) or phosphatidylinositol 3,4, 5-trisphosphate (PtdIns(3,4,5)P3). In mammalian cells, this family contains a series of distinct genes and splice variants. All inositol polyphosphate 5-Phosphatases share a 5-Phosphatase domain and various protein modules probably responsible for specific cell localisation or recruitment (SH2 domain, proline-rich sequences, prenylation sites, etc.). Type I Ins(1,4,5)P3 5-Phosphatase also uses Ins(1,3,4,5)P4 but not the phosphoinositides as substrates. This enzyme is targeted to specific membranes by means of a prenylation site. Type II 5-Phosphatases can use both PtdIns(4,5)P2 and PtdIns(3,4,5)P3 as substrates. Five mammalian enzymes and multiple splice variants are known: INPP5P or inositol polyphosphate 5-Phosphatase II, OCRL (a Golgi protein implicated in the Lowe oculocerebrorenal syndrome), synaptojanin (a protein involved in the recycling of synaptic vesicles), SHIP 1 and SHIP 2 (or SH2-containing inositol 5-Phosphatases). As discussed in this review, the substrate specificity, regulatory mechanisms, subcellular localisation and tissue specificity indicate that the different 5-Phosphatase isoforms may play specific roles. As known in the dephosphorylation of tyrosine containing substrates by the tyrosine protein Phosphatases or in the metabolism of cyclic nucleotides by the cyclic nucleotide phosphodiesterases, inositol polyphosphate 5-Phosphatases directly participate in the control of second messengers in response to both activation or inhibitory cell signalling.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe