scholarly journals MKP-3, a Novel Cytosolic Protein-tyrosine Phosphatase That Exemplifies a New Class of Mitogen-activated Protein Kinase Phosphatase

1996 ◽  
Vol 271 (8) ◽  
pp. 4319-4326 ◽  
Author(s):  
Marco Muda ◽  
Ursula Boschert ◽  
Robin Dickinson ◽  
Jean-Claude Martinou ◽  
Isabelle Martinou ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Mitogen Activated Protein Kinase ◽  
Protein Tyrosine ◽  
New Class ◽  
Cytosolic Protein ◽  
Mitogen Activated Protein

scholarly journals hVH-5: A Protein Tyrosine Phosphatase Abundant in Brain that Inactivates Mitogen-Activated Protein Kinase

2002 ◽  
Vol 65 (4) ◽  
pp. 1823-1833 ◽  
Author(s):  
Karen J. Martell ◽  
Audrey F. Seasholtz ◽  
Seung P. Kwak ◽  
Kristina K. Clemens ◽  
Jack E. Dixon
Keyword(s):  
Protein Kinase ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Mitogen Activated Protein Kinase ◽  
Protein Tyrosine ◽  
Mitogen Activated Protein

scholarly journals Regulation of the Saccharomyces cerevisiae HOG1 mitogen-activated protein kinase by the PTP2 and PTP3 protein tyrosine phosphatases.

1997 ◽  
Vol 17 (3) ◽  
pp. 1289-1297 ◽  
Author(s):  
S M Wurgler-Murphy ◽  
T Maeda ◽  
E A Witten ◽  
H Saito
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Kinase ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Mitogen Activated Protein Kinase ◽  
Yeast Cells ◽  
High Osmolarity ◽  
Mapk Kinase ◽  
Protein Tyrosine ◽  
Mitogen Activated Protein

In response to increases in extracellular osmolarity, Saccharomyces cerevisiae activates the HOG1 mitogen-activated protein kinase (MAPK) cascade, which is composed of a pair of redundant MAPK kinase kinases, namely, Ssk2p and Ssk22p, the MAPK kinase Pbs2p, and the MAPK Hog1p. Hog1p is activated by Pbs2p through phosphorylation of specific threonine and tyrosine residues. Activated Hog1p is essential for survival of yeast cells at high osmolarity. However, expression of constitutively active mutant kinases, such as those encoded by SSK2deltaN and PBS2(DD), is toxic and results in a lethal level of Hog1p activation. Overexpression of the protein tyrosine phosphatase Ptp2p suppresses the lethality of these mutations by dephosphorylating Hog1p. A catalytically inactive Cys-to-Ser Ptp2p mutant (Ptp2(C/S)p) is tightly bound to tyrosine-phosphorylated Hog1p in vivo. Disruption of PTP2 leads to elevated levels of tyrosine-phosphorylated Hog1p following exposure of cells to high osmolarity. Disruption of both PTP2 and another protein tyrosine phosphatase gene, PTP3, results in constitutive Hog1p tyrosine phosphorylation even in the absence of increased osmolarity. Thus, Ptp2p and Ptp3p are the major phosphatases responsible for the tyrosine dephosphorylation of Hog1p. When catalytically inactive Hog1(K/N)p is expressed in hog1delta cells, it is constitutively tyrosine phosphorylated. In contrast, Hog1(K/N)p, expressed together with wild-type Hog1p, is tyrosine phosphorylated only when cells are exposed to high osmolarity. Thus, the kinase activity of Hog1p is required for its own tyrosine dephosphorylation. Northern blot analyses suggest that Hog1p regulates Ptp2p and/or Ptp3p activity at the posttranscriptional level.

Adenosine induces endothelial apoptosis by activating protein tyrosine phosphatase: a possible role of p38α

2000 ◽  
Vol 279 (4) ◽  
pp. L733-L742 ◽  
Author(s):  
Elizabeth O. Harrington ◽  
Anthony Smeglin ◽  
Nancy Parks ◽  
Julie Newton ◽  
Sharon Rounds
Keyword(s):  
Protein Kinase ◽  
Protein Tyrosine Phosphatase ◽  
Intracellular Signaling ◽  
Kinase Inhibitor ◽  
Tyrosine Phosphatase ◽  
Mitogen Activated Protein Kinase ◽  
Adenosylhomocysteine Hydrolase ◽  
Protein Tyrosine ◽  
Mitogen Activated Protein ◽  
Induced Apoptosis

Endothelial cell (EC) apoptosis is important in vascular injury, repair, and angiogenesis. Homocysteine and/or adenosine exposure of ECs causes apoptosis. Elevated homocysteine or adenosine occurs in disease states such as homocysteinuria and tissue necrosis, respectively. We examined the intracellular signaling mechanisms involved in this pathway of EC apoptosis. Inhibition of protein tyrosine phosphatase (PTPase) attenuated homocysteine- and/or adenosine-induced apoptosis and completely blocked apoptosis induced by the inhibition of S-adenosylhomocysteine hydrolase with MDL-28842. Consistent with this finding, the tyrosine kinase inhibitor genistein enhanced apoptosis in adenosine-treated ECs. Adenosine significantly elevated the PTPase activity in the ECs. Mitogen-activated protein kinase activities were examined to identify possible downstream targets for the upregulated PTPase(s). Extracellular signal-regulated kinase (ERK) 1 activity was slightly elevated in adenosine-treated ECs, whereas ERK2, c-Jun NH2-terminal kinase-1, or p38β activities differed little. The mitogen-activated protein kinase-1 inhibitor PD-98059 enhanced DNA fragmentation, suggesting that increased ERK1 activity is a result but not a cause of apoptosis in adenosine-treated ECs. Adenosine-treated ECs had diminished p38α activity compared with control cells; this effect was blunted on PTPase inhibition. These results indicate that PTPase(s) plays an integral role in the induction of EC apoptosis upon exposure to homocysteine and/or adenosine, possibly by the attenuation of p38α activity.

scholarly journals The T-cell protein tyrosine phosphatase is phosphorylated on Ser-304 by cyclin-dependent protein kinases in mitosis

2004 ◽  
Vol 380 (3) ◽  
pp. 939-949 ◽  
Author(s):  
Patricia BUKCZYNSKA ◽  
Manuela KLINGLER-HOFFMANN ◽  
Kenneth I. MITCHELHILL ◽  
Mark H. C. LAM ◽  
Melissa CICCOMANCINI ◽  
...  
Keyword(s):  
T Cell ◽  
Protein Kinase ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Phosphorylation Site ◽  
Protein Kinase Inhibitors ◽  
Mitogen Activated Protein Kinase ◽  
Cell Protein ◽  
Protein Tyrosine ◽  
Dependent Protein

Two alternatively spliced forms of the human protein tyrosine phosphatase TCPTP (T-cell protein tyrosine phosphatase) exist: a 48 kDa form that is targeted to the endoplasmic reticulum (TC48) and a shorter 45 kDa form that is targeted to the nucleus (TC45). In this study we have identified Ser-304 (Phe301-Asp-His-Ser304-Pro-Asn-Lys307) as a major TCPTP phosphory-lation site and demonstrate that TC45, but not TC48, is phosphorylated on this site in vivo. Phosphorylation of TC45 on Ser-304 was cell cycle-dependent, and increased as cells progressed from G2 into mitosis, but subsided upon mitotic exit. Ser-304 phosphorylation was increased when cells were arrested in mitosis by microtubule poisons such as nocodazole, but remained unaltered when cells were arrested at the G2/M checkpoint by adriamycin. Phosphorylation of Ser-304 did not alter significantly the phosphatase activity or the protein stability of TC45, and had no apparent effect on TC45 localization. Ser-304 phosphorylation was ablated when cells were treated with the CDK (cyclin-dependent protein kinase) inhibitors roscovitine or SU9516, but remained unaltered when ERK1/2 activation was inhibited with the MEK (mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase) inhibitor PD98059. In addition, recombinant CDKs, but not the Polo-like kinase Plk1, phosphorylated Ser-304 in vitro. Our studies identify Ser-304 as a major phosphorylation site in human TCPTP, and the TC45 variant as a novel mitotic CDK substrate.

Sign in / Sign up

Export Citation Format

Share Document