Sodium arsenite induces chromosome endoreduplication and inhibits protein phosphatase activity in human fibroblasts

1995 ◽  
Vol 25 (3) ◽  
pp. 188-196 ◽  
Author(s):  
Rong-Nan Huang ◽  
I-Ching Ho ◽  
Ling-Hui Yih ◽  
Te-Chang Lee
Keyword(s):  
Phosphatase Activity ◽  
Protein Phosphatase ◽  
Sodium Arsenite ◽  
Human Fibroblasts ◽  
Chromosome Endoreduplication

scholarly journals Involvement of a phosphotyrosine protein phosphatase in the suppression of platelet-derived growth factor receptor autophosphorylation in ras-transformed cells

1993 ◽  
Vol 293 (1) ◽  
pp. 215-221 ◽  
Author(s):  
L Tomáska ◽  
R J Resnick
Keyword(s):  
Growth Factor ◽  
Phosphatase Activity ◽  
Receptor Tyrosine Kinase ◽  
Protein Phosphatase ◽  
Kinase Activity ◽  
Platelet Derived Growth Factor ◽  
Transformed Cells ◽  
Pdgf Receptor ◽  
Tyrosine Kinase Activity ◽  
Phosphotyrosine Protein Phosphatase

The nature of the suppression of platelet-derived growth factor (PDGF) receptor autophosphorylation in ras-transformed NIH 3T3 fibroblasts was investigated. The PDGF receptor from ras-transformed cells that had been purified by wheatgerm-lectin affinity chromatography displayed normal PDGF-induced autophosphorylation, indicating that the receptor is not irreversibly modified. Various phosphotyrosine-protein-phosphatase inhibitors did not reverse the inhibition of PDGF-receptor kinase in crude membrane preparations from ras-transformed cells. However, treatment of intact ras-transformed cells both with 2 mM sodium orthovanadate and with 20 microM phenylarsine oxide restored PDGF-receptor tyrosine-kinase activity to a level similar to that observed in normal cells. Direct measurement of the phosphatase activities in crude cellular fractions revealed a 2.5-fold higher membrane-associated phosphotyrosine-protein-phosphatase activity in ras-transformed cells, whereas phosphoserine-protein-phosphatase activity remained unchanged between the cell lines. These data suggest that the suppression of the PDGF-receptor tyrosine-kinase activity in ras-transformed cells is mediated via an inhibitory component, distinct from the receptor, that may be positively regulated by the dephosphorylation of tyrosine residue(s).

scholarly journals Insulin-receptor phosphotyrosyl-protein phosphatases

1988 ◽  
Vol 256 (3) ◽  
pp. 893-902 ◽  
Author(s):  
M J King ◽  
G J Sale
Keyword(s):  
Insulin Receptor ◽  
Phosphatase Activity ◽  
Rat Liver ◽  
Protein Phosphatase ◽  
Egf Receptor ◽  
Soluble Fraction ◽  
Protein Phosphatases ◽  
Egf Receptors ◽  
Cell Extracts ◽  
Dependent Protein

Calmodulin-dependent protein phosphatase has been proposed to be an important phosphotyrosyl-protein phosphatase. The ability of the enzyme to attack autophosphorylated insulin receptor was examined and compared with the known ability of the enzyme to act on autophosphorylated epidermal-growth-factor (EGF) receptor. Purified calmodulin-dependent protein phosphatase was shown to catalyse the complete dephosphorylation of phosphotyrosyl-(insulin receptor). When compared at similar concentrations, 32P-labelled EGF receptor was dephosphorylated at greater than 3 times the rate of 32P-labelled insulin receptor; both dephosphorylations exhibited similar dependence on metal ions and calmodulin. Native phosphotyrosyl-protein phosphatases in cell extracts were also characterized. With rat liver, heart or brain, most (75%) of the native phosphatase activity against both 32P-labelled insulin and EGF receptors was recovered in the particulate fraction of the cell, with only 25% in the soluble fraction. This subcellular distribution contrasts with results of previous studies using artificial substrates, which found most of the phosphotyrosyl-protein phosphatase activity in the soluble fraction of the cell. Properties of particulate and soluble phosphatase activity against 32P-labelled insulin and EGF receptors are reported. The contribution of calmodulin-dependent protein phosphatase activity to phosphotyrosyl-protein phosphatase activity in cell fractions was determined by utilizing the unique metal-ion dependence of calmodulin-dependent protein phosphatase. Whereas Ni2+ (1 mM) markedly activated the calmodulin-dependent protein phosphatase, it was found to inhibit potently both particulate and soluble phosphotyrosyl-protein phosphatase activity. In fractions from rat liver, brain and heart, total phosphotyrosyl-protein phosphatase activity against both 32P-labelled receptors was inhibited by 99.5 +/- 6% (mean +/- S.E.M., 30 observations) by Ni2+. Results of Ni2+ inhibition studies were confirmed by other methods. It is concluded that in cell extracts phosphotyrosyl-protein phosphatases other than calmodulin-dependent protein phosphatase are the major phosphotyrosyl-(insulin receptor) and -(EGF receptor) phosphatases.

Inhibition of membrane phosphotyrosyl-protein phosphatase activity by vanadate

1982 ◽  
Vol 107 (3) ◽  
pp. 1104-1109 ◽  
Author(s):  
Ghanshyam Swarup ◽  
Stanley Cohen ◽  
David L. Garbers
Keyword(s):  
Phosphatase Activity ◽  
Protein Phosphatase

scholarly journals Coxiella burnetii inhibits host immunity by a protein phosphatase adapted from glycolysis

2021 ◽  
Vol 119 (1) ◽  
pp. e2110877119
Author(s):  
Yong Zhang ◽  
Jiaqi Fu ◽  
Shuxin Liu ◽  
Lidong Wang ◽  
Jiazhang Qiu ◽  
...  
Keyword(s):  
Phosphatase Activity ◽  
Coxiella Burnetii ◽  
Protein Phosphatase ◽  
Bacterial Pathogen ◽  
Sugar Metabolism ◽  
Host Immunity ◽  
Host Cells ◽  
Functional Screening ◽  
Type Iv ◽  
Fructose 1,6 Bisphosphate

Coxiella burnetii is a bacterial pathogen that replicates within host cells by establishing a membrane-bound niche called the Coxiella-containing vacuole. Biogenesis of this compartment requires effectors of its Dot/Icm type IV secretion system. A large cohort of such effectors has been identified, but the function of most of them remain elusive. Here, by a cell-based functional screening, we identified the effector Cbu0513 (designated as CinF) as an inhibitor of NF-κB signaling. CinF is highly similar to a fructose-1,6-bisphosphate (FBP) aldolase/phosphatase present in diverse bacteria. Further study reveals that unlike its ortholog from Sulfolobus tokodaii, CinF does not exhibit FBP phosphatase activity. Instead, it functions as a protein phosphatase that specifically dephosphorylates and stabilizes IκBα. The IκBα phosphatase activity is essential for the role of CinF in C. burnetii virulence. Our results establish that C. burnetii utilizes a protein adapted from sugar metabolism to subvert host immunity.

scholarly journals A Novel Interaction of the Catalytic Subunit of Protein Phosphatase 2A with the Adaptor Protein CIN85 Suppresses Phosphatase Activity and Facilitates Platelet Outside-in αIIbβ3 Integrin Signaling

2016 ◽  
Vol 291 (33) ◽  
pp. 17360-17368 ◽  
Author(s):  
Tanvir Khatlani ◽  
Subhashree Pradhan ◽  
Qi Da ◽  
Tanner Shaw ◽  
Vladimir L. Buchman ◽  
...  
Keyword(s):  
Phosphatase Activity ◽  
Protein Interactions ◽  
Protein Phosphatase ◽  
Thrombus Formation ◽  
Protein Phosphatase 2A ◽  
Adaptor Protein ◽  
Fibrin Clot ◽  
Catalytic Subunit ◽  
Clot Retraction ◽  
Phosphatase 2A

The transduction of signals generated by protein kinases and phosphatases are critical for the ability of integrin αIIbβ3 to support stable platelet adhesion and thrombus formation. Unlike kinases, it remains unclear how serine/threonine phosphatases engage the signaling networks that are initiated following integrin ligation. Because protein-protein interactions form the backbone of signal transduction, we searched for proteins that interact with the catalytic subunit of protein phosphatase 2A (PP2Ac). In a yeast two-hybrid study, we identified a novel interaction between PP2Ac and an adaptor protein CIN85 (Cbl-interacting protein of 85 kDa). Truncation and alanine mutagenesis studies revealed that PP2Ac binds to the P3 block (396PAIPPKKPRP405) of the proline-rich region in CIN85. The interaction of purified PP2Ac with CIN85 suppressed phosphatase activity. Human embryonal kidney 293 αIIbβ3 cells overexpressing a CIN85 P3 mutant, which cannot support PP2Ac binding, displayed decreased adhesion to immobilized fibrinogen. Platelets contain the ∼85 kDa CIN85 protein along with the PP2Ac-CIN85 complex. A myristylated cell-permeable peptide derived from residues 395–407 of CIN85 protein (P3 peptide) disrupted the platelet PP2Ac-CIN85 complex and decreased αIIbβ3 signaling dependent functions such as platelet spreading on fibrinogen and thrombin-mediated fibrin clot retraction. In a phospho-profiling study P3 peptide treated platelets also displayed decreased phosphorylation of several signaling proteins including Src and GSK3β. Taken together, these data support a role for the novel PP2Ac-CIN85 complex in supporting integrin-dependent platelet function by dampening the phosphatase activity.

Sign in / Sign up

Export Citation Format

Share Document