Protein phosphatase 2A impairs IFNα-induced antiviral activity against the hepatitis C virus through the inhibition of STAT1 tyrosine phosphorylation

2013 ◽  
Vol 20 (9) ◽  
pp. 612-621 ◽  
Author(s):  
V. Shanker ◽  
G. Trincucci ◽  
H. M. Heim ◽  
H. T. F. Duong
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Tyrosine Phosphorylation ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Phosphatase 2A

The protein phosphatase 2A represents a novel cellular target for hepatitis C virus NS5A protein

Biochimie ◽  
2006 ◽  
Vol 88 (6) ◽  
pp. 651-662 ◽  
Author(s):  
Urania Georgopoulou ◽  
Panagiota Tsitoura ◽  
Maria Kalamvoki ◽  
Penelope Mavromara
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Ns5a Protein ◽  
Cellular Target ◽  
Phosphatase 2A

Hepatitis C virus inhibits interferon signaling through up-regulation of protein phosphatase 2A

2004 ◽  
Vol 126 (1) ◽  
pp. 263-277 ◽  
Author(s):  
Francois H.T. Duong ◽  
Magdalena Filipowicz ◽  
Marco Tripodi ◽  
Nicola La Monica ◽  
Markus H. Heim
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Interferon Signaling ◽  
Phosphatase 2A

Virus-induced over-expression of protein phosphatase 2A inhibits insulin signalling in chronic hepatitis C

2008 ◽  
Vol 49 (3) ◽  
pp. 429-440 ◽  
Author(s):  
Christine Bernsmeier ◽  
Francois H.T. Duong ◽  
Verena Christen ◽  
Paolo Pugnale ◽  
Francesco Negro ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Protein Phosphatase ◽  
Insulin Signalling ◽  
Protein Phosphatase 2A ◽  
Over Expression ◽  
Phosphatase 2A

scholarly journals Role of Janus kinase-2 in insulin-mediated phosphorylation and inactivation of protein phosphatase-2A and its impact on upstream insulin signalling components

1999 ◽  
Vol 344 (3) ◽  
pp. 895-901 ◽  
Author(s):  
Najma BEGUM ◽  
Louis RAGOLIA
Keyword(s):  
Tyrosine Phosphorylation ◽  
Protein Phosphatase ◽  
Insulin Treatment ◽  
Insulin Signalling ◽  
Protein Phosphatase 2A ◽  
Catalytic Subunit ◽  
Janus Kinase ◽  
Receptor Protein ◽  
Phosphatase 2A

Our recent studies indicate that insulin rapidly inactivates serine/threonine protein phosphatase-2A (PP-2A) by increasing tyrosine phosphorylation on the catalytic subunit. The exact mechanism of PP-2A inactivation by insulin in vivo is unclear. The Janus kinase (JAK) family of non-receptor protein tyrosine kinases constitute a novel type of signal-transduction pathway which is activated in response to a wide variety of polypeptide ligands, including insulin. In this study we investigated the potential role of JAK-2 in insulin-mediated tyrosine phosphorylation and inactivation of PP-2A using the rat skeletal muscle cell line L6. Co-immunoprecipitation studies revealed that PP-2A is associated with JAK-2 in the basal state. Insulin treatment did not alter JAK-2 association with PP-2A, but did increase JAK-2-mediated tyrosine phosphorylation of the PP-2A catalytic subunit and therefore inhibited PP-2A enzymic activity. Furthermore, PP-2A is associated with phosphoinositide 3-kinase (PI-3K) in the basal state and insulin treatment increases the catalytic activity of PI-3K bound to PP-2A. Pretreatment with AG-490, a specific JAK-2 inhibitor, and SpcAMP, a cAMP agonist, prevented the insulin-mediated increase in (i) JAK-2 kinase activity, (ii) PP-2A tyrosine phosphorylation, (iii) PP-2A inactivation and restored the enzyme activity to control levels, and (iv) PP-2A and JAK-2-associated PI-3K activity. These observations, together with the fact that insulin rapidly activates JAK-2 in L6 cells, and that this is accompanied by an increase in tyrosine phosphorylation of PP-2A in JAK-2 immunoprecipitates, suggest that insulin controls the activation status of PP-2A by tyrosine phosphorylation via JAK-2. PP-2A inactivation may result in an amplification of insulin-generated signals at the level of PI-3K.

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