Inhibitors of protein phosphatase type 1 and 2A attenuate phosphatidylinositol metabolism and calcium-transients in human platelets. Role of a cdc2-related protein kinase

Biochemistry ◽  
1992 ◽  
Vol 31 (28) ◽  
pp. 6553-6561 ◽  
Author(s):  
Kenneth M. Lerea
Keyword(s):  
Protein Kinase ◽  
Protein Phosphatase ◽  
Human Platelets ◽  
Calcium Transients ◽  
Related Protein ◽  
Protein Phosphatase Type 1 ◽  
Phosphatidylinositol Metabolism ◽  
Protein Phosphatase Type

Phosphorylation of the Protein Phosphatase Type 1 Inhibitor Protein CPI-17 by Protein Kinase C

2007 ◽  
pp. 209-224 ◽  
Author(s):  
Michael P. Walsh ◽  
Marija Susnjar ◽  
Jingti Deng ◽  
Cindy Sutherland ◽  
Eniko Kiss ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Phosphatase ◽  
Inhibitor Protein ◽  
Kinase C ◽  
Protein Phosphatase Type 1 ◽  
Protein Phosphatase Type

scholarly journals Functional Analysis of the Yeast Glc7-Binding Protein Reg1 Identifies a Protein Phosphatase Type 1-Binding Motif as Essential for Repression of ADH2 Expression

1999 ◽  
Vol 19 (9) ◽  
pp. 6029-6040 ◽  
Author(s):  
Kenneth M. Dombek ◽  
Valentina Voronkova ◽  
Alexa Raney ◽  
Elton T. Young
Keyword(s):  
Protein Kinase ◽  
Central Region ◽  
Protein Phosphatase ◽  
Kinase Activity ◽  
Protein Kinase Activity ◽  
Snf1 Kinase ◽  
Protein Phosphatase Type 1 ◽  
Mutant Cells ◽  
Protein Phosphatase Type

ABSTRACT In Saccharomyces cerevisiae, the protein phosphatase type 1 (PP1)-binding protein Reg1 is required to maintain complete repression of ADH2 expression during growth on glucose. Surprisingly, however, mutant forms of the yeast PP1 homologue Glc7, which are unable to repress expression of another glucose-regulated gene, SUC2, fully repressed ADH2. ConstitutiveADH2 expression in reg1 mutant cells did require Snf1 protein kinase activity like constitutive SUC2expression and was inhibited by unregulated cyclic AMP-dependent protein kinase activity like ADH2 expression in derepressed cells. To further elucidate the functional role of Reg1 in repressingADH2 expression, deletions scanning the entire length of the protein were analyzed. Only the central region of the protein containing the putative PP1-binding sequence RHIHF was found to be indispensable for repression. Introduction of the I466M F468A substitutions into this sequence rendered Reg1 almost nonfunctional. Deletion of the central region or the double substitution prevented Reg1 from significantly interacting with Glc7 in two-hybrid analyses. Previous experimental evidence had indicated that Reg1 might target Glc7 to nuclear substrates such as the Snf1 kinase complex. Subcellular localization of a fully functional Reg1-green fluorescent protein fusion, however, indicated that Reg1 is cytoplasmic and excluded from the nucleus independently of the carbon source. When the level of Adr1 was modestly elevated, ADH2 expression was no longer fully repressed in glc7 mutant cells, providing the first direct evidence that Glc7 can repress ADH2 expression. These results suggest that the Reg1-Glc7 phosphatase is a cytoplasmic component of the machinery responsible for returning Snf1 kinase activity to its basal level and reestablishing glucose repression. This implies that the activated form of the Snf1 kinase complex must cycle between the nucleus and the cytoplasm.

scholarly journals Regulation of acrosome reaction of fowl spermatozoa: evidence for the involvement of protein kinase C and protein phosphatase-type 1 and/or -type 2A

Reproduction ◽  
2006 ◽  
Vol 131 (6) ◽  
pp. 1017-1024 ◽  
Author(s):  
K Ashizawa ◽  
G J Wishart ◽  
S Katayama ◽  
D Takano ◽  
A R A H Ranasinghe ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Okadaic Acid ◽  
Protein Phosphatase ◽  
Acrosome Reaction ◽  
Dependent Manner ◽  
Kinase C ◽  
Protein Phosphatase Type 1 ◽  
Protein Phosphatase Type

The signal transduction pathways involved in the regulation of the acrosome reaction and motility of fowl spermatozoa were investigated. The motility and acrosomal integrity of fowl spermatozoa in TES/NaCl buffer, with or without homogenised inner perivitelline layers (IPVL), prepared from laid fowl eggs, was almost negligible at 40 °C. In the presence of 2 mmol CaCl2/l at 40 °C, motility became vigorous and the acrosome reaction was stimulated when IPVL was added. In the absence of Ca2+, motility was stimulated by the addition of calyculin A and okadaic acid, both specific inhibitors of protein phosphatase-type 1 (PP1) and -type 2A (PP2A), but Okadaic acid, which is a weaker inhibitor of PP1, did not completely restore motility at 40 °C. However, the acrosome reaction was significantly and equally stimulated in a dose-dependent manner by both inhibitors in the range of 10–1000 nmol/l, when spermatozoa were incubated with IPVL but without Ca2+. These inhibitors did not stimulate the acrosome reaction in the absence of IPVL. The vigorous motility of spermatozoa, stimulated by the addition of Ca2+, was reduced gradually as the concentrations of SC-9, a selective activator of protein kinase C (PKC), were increased and a similar SC-9-induced inhibition was observed in the acrosome reaction in the presence of Ca2+ and IPVL. These results confirm that IPVL is necessary for the activation of the acrosome reaction in fowl spermatozoa and that Ca2+ plays an important role in the stimulation of motility and acrosomal exocytosis. Furthermore, it appears that the intracellular molecular mechanisms for the regulation of acrosome reaction of fowl spermatozoa are different from those for the restoration of motility, i.e., protein dephosporylation involving PP1 and/or PP2A in the former, and PP1 alone in the latter case. In addition, the activation of PKC may contribute to a decrease in the flagellar movement and acrosome reaction of fowl spermatozoa.

scholarly journals Essential role of GEXP15, a specific Protein Phosphatase type 1 partner, in Plasmodium berghei in asexual erythrocytic proliferation and transmission

2019 ◽  
Vol 15 (7) ◽  
pp. e1007973 ◽  
Author(s):  
Thomas Hollin ◽  
Caroline De Witte ◽  
Aline Fréville ◽  
Ida Chiara Guerrera ◽  
Cerina Chhuon ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Protein Phosphatase ◽  
Essential Role ◽  
Specific Protein ◽  
Protein Phosphatase Type 1 ◽  
Protein Phosphatase Type

scholarly journals Inhibitor-2 prevents protein phosphatase 1-induced cardiac hypertrophy and mortality

2008 ◽  
Vol 295 (4) ◽  
pp. H1539-H1546 ◽  
Author(s):  
Nicole Brüchert ◽  
Nirmala Mavila ◽  
Peter Boknik ◽  
Hideo A. Baba ◽  
Larissa Fabritz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Protein Phosphatase ◽  
Cardiac Fibrosis ◽  
Heart Function ◽  
Premature Death ◽  
Protein Phosphatase Type 1 ◽  
Age Dependent ◽  
Protein Phosphatase Type

Cardiac-specific overexpression of the catalytic subunit of protein phosphatase type 1 (PP1) in mice results in hypertrophy, depressed contractility, propensity to heart failure, and premature death. To further address the role of PP1 in heart function, PP1 mice were crossed with mice that overexpress a functional COOH-terminally truncated form of PP1 inhibitor-2 (I-2140). Protein phosphatase activity was increased in PP1 mice but was normalized in double transgenic (DT) mice. The maximal rates of contraction (+dP/d t) and of relaxation (−dP/d t) were reduced in catheterized PP1 mice but normalized in DT mice. Similar contractile abnormalities were observed in isolated, perfused work-performing hearts and in whole animals by means of echocardiography. The increased absolute and relative heart weights observed in PP1 mice were normalized in DT mice. Histological analyses indicated that PP1 mice had significant cardiac fibrosis, which was absent in DT mice. Furthermore, PP1 mice exhibited an age-dependent increase in mortality, which was abrogated in DT mice. These results indicate that I-2 overexpression prevents the detrimental effects of PP1 overexpression in the heart and further underscore the fundamental role of PP1 in cardiac function. Therefore, PP1 inhibitors such as I-2 could offer new therapeutic options to ameliorate the deleterious effects of heart failure.

scholarly journals Ectopic Expression of Inhibitors of Protein Phosphatase Type 1 (PP1) Can Be Used to Analyze Roles of PP1 in Drosophila Development

Genetics ◽  
2003 ◽  
Vol 164 (1) ◽  
pp. 235-245
Author(s):  
Daimark Bennett ◽  
Balázs Szöőr ◽  
Sascha Gross ◽  
Natalia Vereshchagina ◽  
Luke Alphey
Keyword(s):  
Protein Phosphatase ◽  
Muscle Development ◽  
Ectopic Expression ◽  
High Specificity ◽  
Type I ◽  
Protein Phosphatase Type 1 ◽  
Mitotic Figures ◽  
Protein Phosphatase Type

Abstract We have identified two proteins that bind with high specificity to type 1 serine/threonine protein phosphatase (PP1) and have exploited their inhibitory properties to develop an efficient and flexible strategy for conditional inactivation of PP1 in vivo. We show that modest overexpression of Drosophila homologs of I-2 and NIPP1 (I-2Dm and NIPP1Dm) reduces the level of PP1 activity and phenotypically resembles known PP1 mutants. These phenotypes, which include lethality, abnormal mitotic figures, and defects in muscle development, are suppressed by coexpression of PP1, indicating that the effect is due specifically to loss of PP1 activity. Reactivation of I-2Dm:PP1c complexes suggests that inhibition of PP1 activity in vivo does not result in a compensating increase in synthesis of active PP1. PP1 mutants enhance the wing overgrowth phenotype caused by ectopic expression of the type II TGFβ superfamily signaling receptor Punt. Using I-2Dm, which has a less severe effect than NIPP1Dm, we show that lowering the level of PP1 activity specifically in cells overexpressing Punt is sufficient for wing overgrowth and that the interaction between PP1 and Punt requires the type I receptor Thick-veins (Tkv) but is not strongly sensitive to the level of the ligand, Decapentaplegic (Dpp), nor to that of the other type I receptors. This is consistent with a role for PP1 in antagonizing Punt by preventing phosphorylation of Tkv. These studies demonstrate that inhibitors of PP1 can be used in a tissue- and developmental-specific manner to examine the developmental roles of PP1.

Differential expression of protein phosphatase type 1 isotypes and nucleolin during cell cycle arrest

2007 ◽  
Vol 25 (4) ◽  
pp. 369-375 ◽  
Author(s):  
Hiroyuki Morimoto ◽  
Akiko Ozaki ◽  
Hirohiko Okamura ◽  
Kaya Yoshida ◽  
Bruna Rabelo Amorim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Differential Expression ◽  
Protein Phosphatase ◽  
Cycle Arrest ◽  
Protein Phosphatase Type 1 ◽  
Protein Phosphatase Type
Sign in / Sign up

Export Citation Format

Share Document