scholarly journals Regulation of membrane-associated tyrosine phosphatases in UMR 106.06 osteoblast-like cells

1995 ◽  
Vol 305 (2) ◽  
pp. 485-490 ◽  
Author(s):  
M C Southey ◽  
D M Findlay ◽  
B E Kemp
Keyword(s):  
Growth Factor ◽  
Molecular Mass ◽  
Phosphatase Activity ◽  
Cell Density ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Apparent Molecular Mass ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine

Protein tyrosine phosphatases play an important role in cell metabolism. Three distinct protein tyrosine phosphatase activities have been identified in an osteoblast-like cell line, UMR 106.06. These activities comprised two membrane-associated phosphatases and one cytosolic phosphatase of apparent molecular mass > 153 kDa, 80 kDa and 40 kDa respectively, estimated by gel filtration. On the basis of differences in apparent molecular mass, proteolytic-digestion profiles, substrate specificities and responses to a range of extracellular influences and inhibitor molecules, the two membrane-associated tyrosine phosphatases are distinct proteins. Tyrosine phosphatase activity in UMR 106.06 cells was sensitive to cell density. Cells at confluence contained membrane protein tyrosine phosphatase with specific activity 9-fold higher than cells at medium or low cell density. This elevation in membrane tyrosine phosphatase activity was due specifically to an increase in the high-molecular-mass enzyme. This phosphatase was also responsive to extracellular matrix components. This activity was elevated in cells grown on a collagen type-I matrix independently of cell density. Membrane and cytosolic protein tyrosine phosphatases were differentially regulated by a variety of agents including phorbol 12-myristate 13-acetate, parathyroid hormone, epidermal growth factor, okadaic acid and transforming growth factor beta. These observations suggest that regulatory influences control tyrosine phosphorylation in UMR 106.06 cells including cell-cell contact, cell-matrix contact and signal transduction involving tyrosine and serine/threonine phosphorylation events.

SRC binding to the cytoskeleton, triggered by growth cone attachment to laminin, is protein tyrosine phosphatase-dependent

1998 ◽  
Vol 111 (16) ◽  
pp. 2465-2475 ◽  
Author(s):  
S. Helmke ◽  
K. Lohse ◽  
K. Mikule ◽  
M.R. Wood ◽  
K.H. Pfenninger
Keyword(s):  
Phosphatase Activity ◽  
Growth Cone ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Growth Cones ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine ◽  
Adhesion Sites ◽  
Adhesion Site

The interaction of the non-receptor tyrosine kinase, Src, with the cytoskeleton of adhesion sites was studied in nerve growth cones isolated from fetal rat brain. Of particular interest was the role of protein tyrosine phosphatases in the regulation of Src-cytoskeleton binding. Growth cones were found to contain a high level of protein tryrosine phosphatase activity, most of it membrane-associated and forming large, multimeric and wheat germ agglutinin-binding complexes. The receptor tyrosine phosphatase PTPalpha seems to be the most prevalent species among the membrane-associated enzymes. As seen by immunofluorescence, PTPalpha is present throughout the plasmalemma of the growth cone including filopodia, and it forms a punctate pattern consistent with that of integrin beta1. For adhesion site analysis, isolated growth cones were either plated onto the neurite growth substratum, laminin, or kept in suspension. Plating growth cones on laminin triggered an 8-fold increase in Src binding to the adherent cytoskeleton. This effect was blocked completely with the protein tyrosine phosphatase inhibitor, vanadate. Growth cone plating also increased the association with adhesion sites of tyrosine phosphatase activity (14-fold) and of PTPalpha immunoreactivity (6-fold). Vanadate blocked the enzyme activity but not the recruitment of PTPalpha to the adhesion sites. In conjunction with our previous results on growth cones, these data suggest that integrin binding to laminin triggers the recruitment of PTPalpha (and perhaps other protein tyrosine phosphatases) to adhesion sites, resulting in de-phosphorylation of Src's tyr 527. As a result Src unfolds, becomes kinase-active, and its SH2 domain can bind to an adhesion site protein. This implies a critical role for protein tyrosine phosphatase activity in the earliest phases of adhesion site assembly.

Protein tyrosine phosphatase activity in human endometrium

2001 ◽  
Vol 13 (3) ◽  
pp. 175 ◽  
Author(s):  
Seppo Partanen
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Phosphatase Activity ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Kinases ◽  
Tyrosine Phosphatase ◽  
Intrauterine Device ◽  
Human Endometrium ◽  
Protein Tyrosine ◽  
Glandular Cells

Protein tyrosine phosphatase (PTP) activity was demonstrated in human endometrium by a histochemical method using phosphotyrosine as substrate. For comparative purposes, non-specific acid phosphatase (AcP) activity was also examined. Protein tyrosine phosphatase activity was very low in proliferative and atrophic endometrium, but its activity was increased 9-fold in glandular epithelium during the secretory phase, and 48-fold in predecidual endometrium, induced by a progestagen-releasing intrauterine device, compared with the proliferative endometrium. Thus, PTP activity appeared to be progesterone-induced. Endometrial PTP appeared to be cellular rather than secretory in origin; its activity was inhibited by vanadate, and its histochemical properties were different from those of lysosomal AcP, but similar to those of prostatic-type AcP. Endometrial PTP may functionally counteract the effects of protein tyrosine kinases (PTKs) associated with growth factor receptors and cellular oncoproteins. Cyclic endometrial proliferation and differentiation are thought to be regulated by the autocrine and paracrine pathways by growth factors such as epidermal growth factor, insulin-like growth factor I and platelet-derived growth factors, and their receptors. However, cessation of proliferation could not be explained by the amounts of these growth factors present or their receptors, in that no constant changes at the interface of the late proliferative and early secretory phases were found. Down-regulation of stimulatory-signalling pathways of PTKs by endometrial PTP induced by progesterone may explain the decrease observed in proliferative activity of glandular cells in cyclic endometrium.

scholarly journals Protein tyrosine phosphatase containing SH2 domains: characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12-p13.

1992 ◽  
Vol 12 (2) ◽  
pp. 836-846 ◽  
Author(s):  
T L Yi ◽  
J L Cleveland ◽  
J N Ihle
Keyword(s):  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Phosphatase ◽  
Human Gene ◽  
Tyrosine Phosphatase ◽  
Hematopoietic Cells ◽  
Protein Tyrosine Phosphatases ◽  
Hematopoietic Cell ◽  
Protein Tyrosine Phosphorylation ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine

Protein tyrosine phosphorylation has been implicated in the growth and functional responses of hematopoietic cells. Recently, approaches have been developed to characterize the protein tyrosine phosphatases that may contribute to regulation of protein tyrosine phosphorylation. One novel protein tyrosine phosphatase was expressed predominantly in hematopoietic cells. Hematopoietic cell phosphatase encodes a 68-kDa protein that contains a single phosphatase conserved domain. Unlike other known protein tyrosine phosphatases, hematopoietic cell phosphatase contains two src homology 2 domains. We also cloned the human homolog, which has 95% amino acid sequence identity. Both the murine and human gene products have tyrosine-specific phosphatase activity, and both are expressed predominantly in hematopoietic cells. Importantly, the human gene maps to chromosome 12 region p12-p13. This region is associated with rearrangements in approximately 10% of cases of acute lymphocytic leukemia in children.

scholarly journals Structure, mapping, and expression of erp, a growth factor-inducible gene encoding a nontransmembrane protein tyrosine phosphatase, and effect of ERP on cell growth.

1993 ◽  
Vol 13 (9) ◽  
pp. 5195-5205 ◽  
Author(s):  
T Noguchi ◽  
R Metz ◽  
L Chen ◽  
M G Mattéi ◽  
D Carrasco ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phosphatase Activity ◽  
Genomic Structure ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Early Gene ◽  
Structure Mapping ◽  
Significant Similarity ◽  
Protein Tyrosine ◽  
Inducible Gene

We have characterized a growth factor-inducible gene, erp, and demonstrated that it encodes a 367-amino-acid nontransmembrane tyrosine phosphatase protein with significant similarity to the vaccinia virus H1 protein. Immunoprecipitation analyses show that the erp protein, ERP, is rapidly induced following serum stimulation of quiescent fibroblasts. ERP has been expressed as a fusion protein with glutathione S-transferase and shown to have tyrosine as well as serine protein phosphatase activity. The enzymatic activity of ERP depends on the presence of reducing agents such as dithiothreitol, and its tyrosine phosphatase activity is inhibited by sodium vanadate, a potent inhibitor of protein tyrosine phosphatases. The number of stable NIH 3T3 clones obtained after transfection with a vector expressing the complete ERP protein is reduced more than 90% compared with that after transfection with a vector expressing a mutated inactive ERP protein. The remaining ERP-expressing clones present a significant increase in the proportion of bi- and multinucleated cells and a decrease in proliferation rate. Studies on the genomic structure reveal that the erp transcription unit is 2.8 kbp long and split into four exons. The erp gene maps to the 17A2-17C region of the murine genome. Our results demonstrate that the protein product of the immediate-early gene erp has a negative effect on cell proliferation.

scholarly journals Sulfonyl-bridged Calix[4]arene as an Inhibitor of Protein Tyrosine Phosphatases

2017 ◽  
Vol 5 (2) ◽  
pp. 144-151 ◽  
Author(s):  
Vladyslav Buldenko ◽  
Oleksandr Kobzar ◽  
Viacheslav Trush ◽  
Andriy Drapailo ◽  
Vitaly Kalchenko ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine ◽  
Ic50 Value ◽  
Potential Inhibitors ◽  
Derivatives Of ◽  
Active Site Region ◽  
Micromolar Range

Previously, phosphonic acid derivatives of calix[4]arene and thiacalix[4]arene were found to be potential inhibitors of protein tyrosine phosphatase 1B. In the present paper, the inhibitory activity of unsubstituted sulfonyl-bridget calix[4]arene towards some of the therapeutically important protein tyrosine phosphatases has been established. The obtained results showed that the sulfonylcalix[4]arene is able to inhibit protein tyrosine phosphatase MEG2 with IC50 value in the micromolar range. At the same time, the inhibitor demonstrated lower activity in case of other protein tyrosine phosphatases such as PTP1B, MEG1, TC-PTP, SHP2, and PTPβ. The performed molecular docking indicated that the inhibitor binds to the active site region of MEG2 and PTP1B with WPD-loop in the open conformation.

Protein tyrosine phosphatase containing SH2 domains: characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12-p13

1992 ◽  
Vol 12 (2) ◽  
pp. 836-846
Author(s):  
T L Yi ◽  
J L Cleveland ◽  
J N Ihle
Keyword(s):  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Phosphatase ◽  
Human Gene ◽  
Tyrosine Phosphatase ◽  
Hematopoietic Cells ◽  
Protein Tyrosine Phosphatases ◽  
Hematopoietic Cell ◽  
Protein Tyrosine Phosphorylation ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine

Protein tyrosine phosphorylation has been implicated in the growth and functional responses of hematopoietic cells. Recently, approaches have been developed to characterize the protein tyrosine phosphatases that may contribute to regulation of protein tyrosine phosphorylation. One novel protein tyrosine phosphatase was expressed predominantly in hematopoietic cells. Hematopoietic cell phosphatase encodes a 68-kDa protein that contains a single phosphatase conserved domain. Unlike other known protein tyrosine phosphatases, hematopoietic cell phosphatase contains two src homology 2 domains. We also cloned the human homolog, which has 95% amino acid sequence identity. Both the murine and human gene products have tyrosine-specific phosphatase activity, and both are expressed predominantly in hematopoietic cells. Importantly, the human gene maps to chromosome 12 region p12-p13. This region is associated with rearrangements in approximately 10% of cases of acute lymphocytic leukemia in children.

Structure, mapping, and expression of erp, a growth factor-inducible gene encoding a nontransmembrane protein tyrosine phosphatase, and effect of ERP on cell growth

1993 ◽  
Vol 13 (9) ◽  
pp. 5195-5205
Author(s):  
T Noguchi ◽  
R Metz ◽  
L Chen ◽  
M G Mattéi ◽  
D Carrasco ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phosphatase Activity ◽  
Genomic Structure ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Early Gene ◽  
Structure Mapping ◽  
Significant Similarity ◽  
Protein Tyrosine ◽  
Inducible Gene

We have characterized a growth factor-inducible gene, erp, and demonstrated that it encodes a 367-amino-acid nontransmembrane tyrosine phosphatase protein with significant similarity to the vaccinia virus H1 protein. Immunoprecipitation analyses show that the erp protein, ERP, is rapidly induced following serum stimulation of quiescent fibroblasts. ERP has been expressed as a fusion protein with glutathione S-transferase and shown to have tyrosine as well as serine protein phosphatase activity. The enzymatic activity of ERP depends on the presence of reducing agents such as dithiothreitol, and its tyrosine phosphatase activity is inhibited by sodium vanadate, a potent inhibitor of protein tyrosine phosphatases. The number of stable NIH 3T3 clones obtained after transfection with a vector expressing the complete ERP protein is reduced more than 90% compared with that after transfection with a vector expressing a mutated inactive ERP protein. The remaining ERP-expressing clones present a significant increase in the proportion of bi- and multinucleated cells and a decrease in proliferation rate. Studies on the genomic structure reveal that the erp transcription unit is 2.8 kbp long and split into four exons. The erp gene maps to the 17A2-17C region of the murine genome. Our results demonstrate that the protein product of the immediate-early gene erp has a negative effect on cell proliferation.

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