scholarly journals The Attenuated Secretion of Hyaluronan by UVA-Exposed Human Fibroblasts Is Associated with Up- and Downregulation of HYBID and HAS2 Expression via Activated and Inactivated Signaling of the p38/ATF2 and JAK2/STAT3 Cascades

2021 ◽  
Vol 22 (4) ◽  
pp. 2057
Author(s):  
Shuko Terazawa ◽  
Mariko Takada ◽  
Yoriko Sato ◽  
Hiroaki Nakajima ◽  
Genji Imokawa
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Protein Phosphatase ◽  
Tyrosine Phosphatase ◽  
Human Fibroblasts ◽  
Mrna Level ◽  
Dermal Fibroblasts ◽  
Protein Tyrosine ◽  
Protein Levels ◽  
Hyaluronan Binding ◽  
Uva Radiation

Little is known about the effects on hyaluronan (HA) metabolism of UVA radiation. This study demonstrates that the secretion of HA by human dermal fibroblasts (HDFs) is downregulated by UVA, accompanied by the down- and upregulation of mRNA and protein levels of the HA-synthesizing enzyme (HAS2) and the HA-degrading protein, HYaluronan Binding protein Involved in HA Depolymerization(HYBID), respectively. Signaling analysis revealed that the exposure distinctly elicits activation of the p38/MSK1/CREB/c-Fos/AP-1 axis, the JNK/c-Jun axis, and the p38/ATF-2 axis, but downregulates the phosphorylation of NF-kB and JAK/STAT3. A signal inhibition study demonstrated that the inhibition of p38 significantly abrogates the UVA-accentuated mRNA level of HYBID. Furthermore, the inhibition of STAT3 significantly downregulates the level of HAS2 mRNA in non-UVA exposed HDFs. Analysis using siRNAs demonstrated that transfection of ATF-2 siRNA but not c-Fos siRNA abrogates the increased protein level of HYBID in UVA-exposed HDFs. An inhibitor of protein tyrosine phosphatase but not of protein serine/threonine phosphatase restored the diminished phosphorylation level of STAT3 at Tyr 705, accompanied by a significant abolishing effect on the decreased mRNA expression level of HAS2. Silencing with a protein tyrosine phosphatase PTP-Meg2 siRNA revealed that it abrogates the decreased phosphorylation of STAT3 at Tyr 705 in UVA-exposed HDFs. These findings suggest that the UVA-induced decrease in HA secretion by HDFs is attributable to the down- and upregulation of HAS2 and HYBID expression, respectively, changes that are mainly ascribed to the inactivated signaling of the STAT3 axis due to the activated tyrosine protein phosphatase PTP-Meg2 and the activated signaling of the p38/ATF2 axis, respectively.

scholarly journals Mutations in a protein tyrosine phosphatase gene (PTP2) and a protein serine/threonine phosphatase gene (PTC1) cause a synthetic growth defect in Saccharomyces cerevisiae.

1993 ◽  
Vol 13 (9) ◽  
pp. 5408-5417 ◽  
Author(s):  
T Maeda ◽  
A Y Tsai ◽  
H Saito
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Phosphatase Activity ◽  
Protein Tyrosine Phosphatase ◽  
Protein Phosphatase ◽  
Fusion Gene ◽  
Tyrosine Phosphatase ◽  
Growth Defect ◽  
Glutathione S Transferase ◽  
Protein Tyrosine ◽  
Colony Color

Two protein tyrosine phosphatase genes, PTP1 and PTP2, are known in Saccharomyces cerevisiae. However, the functions of these tyrosine phosphatases are unknown, because mutations in either or both phosphatase genes have no clear phenotypic effects. In this report, we demonstrate that although ptp2 has no obvious phenotype by itself, it has a profound effect on cell growth when combined with mutations in a novel protein phosphatase gene. Using a colony color sectoring assay, we isolated 25 mutants in which the expression of PTP1 or PTP2 is required for growth. Complementation tests of the mutants showed that they have a mutation in one of three genes. Cloning and sequence determination of one of these gene, PTC1, indicated that it encodes a homolog of the mammalian protein serine/threonine phosphatase 2C (PP2C). The amino acid sequence of the PTC1 product is approximately 35% identical to PP2C. Disruption of PTC1 indicated that the PTC1 function is nonessential. In contrast, ptc1 ptp2 double mutants showed a marked growth defect. To examine whether PTC1 encodes an active protein phosphatase, a glutathione S-transferase (GST)-PTC1 fusion gene was constructed and expressed in Escherichia coli. Purified GST-PTC1 fusion protein hydrolyzed a serine phosphorylated substrate in the presence of the divalent cation Mg2+ or Mn2+. GST-PTC1 also had weak (approximately 0.5% of its serine phosphatase activity) protein tyrosine phosphatase activity.

Mutations in a protein tyrosine phosphatase gene (PTP2) and a protein serine/threonine phosphatase gene (PTC1) cause a synthetic growth defect in Saccharomyces cerevisiae

1993 ◽  
Vol 13 (9) ◽  
pp. 5408-5417
Author(s):  
T Maeda ◽  
A Y Tsai ◽  
H Saito
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Phosphatase Activity ◽  
Protein Tyrosine Phosphatase ◽  
Protein Phosphatase ◽  
Fusion Gene ◽  
Tyrosine Phosphatase ◽  
Growth Defect ◽  
Glutathione S Transferase ◽  
Protein Tyrosine ◽  
Colony Color

Two protein tyrosine phosphatase genes, PTP1 and PTP2, are known in Saccharomyces cerevisiae. However, the functions of these tyrosine phosphatases are unknown, because mutations in either or both phosphatase genes have no clear phenotypic effects. In this report, we demonstrate that although ptp2 has no obvious phenotype by itself, it has a profound effect on cell growth when combined with mutations in a novel protein phosphatase gene. Using a colony color sectoring assay, we isolated 25 mutants in which the expression of PTP1 or PTP2 is required for growth. Complementation tests of the mutants showed that they have a mutation in one of three genes. Cloning and sequence determination of one of these gene, PTC1, indicated that it encodes a homolog of the mammalian protein serine/threonine phosphatase 2C (PP2C). The amino acid sequence of the PTC1 product is approximately 35% identical to PP2C. Disruption of PTC1 indicated that the PTC1 function is nonessential. In contrast, ptc1 ptp2 double mutants showed a marked growth defect. To examine whether PTC1 encodes an active protein phosphatase, a glutathione S-transferase (GST)-PTC1 fusion gene was constructed and expressed in Escherichia coli. Purified GST-PTC1 fusion protein hydrolyzed a serine phosphorylated substrate in the presence of the divalent cation Mg2+ or Mn2+. GST-PTC1 also had weak (approximately 0.5% of its serine phosphatase activity) protein tyrosine phosphatase activity.

scholarly journals Effect of oxidative stress on protein tyrosine phosphatase 1B in scleroderma dermal fibroblasts

2012 ◽  
Vol 64 (6) ◽  
pp. 1978-1989 ◽  
Author(s):  
Pei-Suen Tsou ◽  
Nadine N. Talia ◽  
Adam J. Pinney ◽  
Ann Kendzicky ◽  
Sonsoles Piera-Velazquez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Dermal Fibroblasts ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine

scholarly journals Crystal structure of protein tyrosine phosphatase-2 from Cydia pomonella granulovirus

2019 ◽  
Vol 75 (4) ◽  
pp. 233-238
Author(s):  
Guangmei Huang ◽  
Michael R. Oliver ◽  
Jeremy R. Keown ◽  
David C. Goldstone ◽  
Peter Metcalf
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Protein Phosphatase ◽  
Tyrosine Phosphatase ◽  
Cydia Pomonella ◽  
Dna Viruses ◽  
Protein Tyrosine ◽  
Viral Genomes ◽  
Homology Groups ◽  
The Third ◽  
Cydia Pomonella Granulovirus

Many viral genomes encode kinase and phosphatase enzymes to manipulate pathways that are controlled by phosphorylation events. The majority of viral phosphatase genes occur in the Baculoviridae and Poxviridae families of large DNA viruses. The corresponding protein sequences belong to four major homology groups, and structures are currently available for only two of these. Here, the first structure from the third group, the protein tyrosine phosphatase-2 (PTP-2) class of viral phosphatases, is described. It is shown that Cydia pomonella granulovirus PTP-2 has the same general fold and active-site architecture as described previously for other phosphatases, in the absence of significant sequence homology. Additionally, it has a novel C-terminal extension in an area corresponding to the interface of dimeric poxvirus phosphatases belonging to the Tyr–Ser protein phosphatase homology group.

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