CK2α — protein phosphatase 2A molecular complex: Possible interaction with the MAP kinase pathway

1999 ◽  
pp. 207-212
Author(s):  
Franck Lebrin ◽  
Laurence Bianchini ◽  
Thierry Rabilloud ◽  
Edmond M. Chambaz ◽  
Yves Goldberg
Keyword(s):  
Map Kinase ◽  
Molecular Complex ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Phosphatase 2A ◽  
Map Kinase Pathway ◽  
Kinase Pathway

scholarly journals The interaction of SV40 small tumor antigen with protein phosphatase 2A stimulates the map kinase pathway and induces cell proliferation

Cell ◽  
1993 ◽  
Vol 75 (5) ◽  
pp. 887-897 ◽  
Author(s):  
Estelle Sontag ◽  
Sergei Fedorov ◽  
Craig Kamibayashi ◽  
David Robbins ◽  
Melanie Cobb ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Map Kinase ◽  
Tumor Antigen ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Small Tumor ◽  
Phosphatase 2A ◽  
Map Kinase Pathway ◽  
Kinase Pathway

scholarly journals Protein Phosphatase 2A Forms a Molecular Complex with Shc and Regulates Shc Tyrosine Phosphorylation and Downstream Mitogenic Signaling

2002 ◽  
Vol 22 (7) ◽  
pp. 2375-2387 ◽  
Author(s):  
Satoshi Ugi ◽  
Takeshi Imamura ◽  
William Ricketts ◽  
Jerrold M. Olefsky
Keyword(s):  
Growth Factor ◽  
Map Kinase ◽  
Tyrosine Phosphorylation ◽  
Protein Phosphatase ◽  
T Antigen ◽  
Phosphatase 2A ◽  
Map Kinase Pathway ◽  
Small T Antigen ◽  
Kinase Pathway ◽  
Ptb Domain

ABSTRACT Protein phosphatase 2A (PP2A) is a multimeric serine/threonine phosphatase that carries out multiple functions. Although numerous observations suggest that PP2A plays a major role in downregulation of the mitogen-activated protein (MAP) kinase pathway, the precise mechanisms are unknown. To clarify the role of PP2A in growth factor (insulin, epidermal growth factor [EGF], and insulin-like growth factor 1 [IGF-1]) stimulation of the Ras/MAP kinase pathway, simian virus 40 small t antigen was expressed in Rat-1 fibroblasts which overexpress insulin receptors. Small t antigen is known to specifically inhibit PP2A by binding to the A PP2A regulatory subunit, interfering with the ability of PP2A to bind to its cellular substrates. Overexpressed small t protein was coimmunoprecipitated with PP2A and inhibited cellular PP2A activity but did not inhibit protein phosphatase 1 (PP1) activity. Insulin, IGF-1, and EGF stimulation also inhibited PP2A activity. Growth factor-stimulated Ras, Raf-1, MAP kinase, and mitogen-activated extracellular-signal-regulated kinase kinase (MEK) activities were elevated in small-t-antigen-expressing cells. Furthermore, Shc tyrosine phosphorylation and its association with Grb2 were also elevated in small-t-antigen-expressing cells. Expression levels of Shc, Ras, MEK, or MAP kinase and phosphorylation of insulin, EGF, and IGF-1 receptors were not altered. Interestingly, we found that PP2A associated with Shc in the basal state and dissociated in response to insulin and EGF and that this dissociation was inhibited by 65% in small-t-antigen-expressing cells. In addition, we found that PP2A associates with the phosphotyrosine-binding domain (PTB domain) of Shc and that phosphorylation of tyrosine 317 of Shc was required for PP2A-Shc dissociation. We conclude (i) that PP2A negatively regulates the Ras/MAP kinase pathway by binding to Shc, inhibiting tyrosine phosphorylation; (ii) that the Shc-PP2A association is mediated by the Shc PTB domain but the interaction is independent of phosphotyrosine binding, indicating a new molecular function for the PTB domain; (iii) that growth factor stimulation, or small-t-antigen expression, causes dissociation of the PP2A-Shc complex, facilitating Shc phosphorylation and downstream activations of the Ras/MAP kinase pathway; and (iv) that this defines a new mechanism of small-t-antigen action to promote mitogenesis.

scholarly journals Protein Phosphatase 2A Negatively Regulates Insulin's Metabolic Signaling Pathway by Inhibiting Akt (Protein Kinase B) Activity in 3T3-L1 Adipocytes

2004 ◽  
Vol 24 (19) ◽  
pp. 8778-8789 ◽  
Author(s):  
Satoshi Ugi ◽  
Takeshi Imamura ◽  
Hiroshi Maegawa ◽  
Katsuya Egawa ◽  
Takeshi Yoshizaki ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Glucose Transport ◽  
Protein Phosphatase ◽  
T Antigen ◽  
Metabolic Signaling ◽  
Phosphatase 2A ◽  
Map Kinase Pathway ◽  
Small T Antigen ◽  
Kinase Pathway

ABSTRACT Protein phosphatase 2A (PP2A) is a multimeric serine/threonine phosphatase which has multiple functions, including inhibition of the mitogen-activated protein (MAP) kinase pathway. Simian virus 40 small t antigen specifically inhibits PP2A function by binding to the PP2A regulatory subunit, interfering with the ability of PP2A to associate with its cellular substrates. We have reported that the expression of small t antigen inhibits PP2A association with Shc, leading to augmentation of insulin and epidermal growth factor-induced Shc phosphorylation with enhanced activation of the Ras/MAP kinase pathway. However, the potential involvement of PP2A in insulin's metabolic signaling pathway is presently unknown. To assess this, we overexpressed small t antigen in 3T3-L1 adipocytes by adenovirus-mediated gene transfer and found that the phosphorylation of Akt and its downstream target, glycogen synthase kinase 3β, were enhanced both in the absence and in the presence of insulin. Furthermore, protein kinase C λ (PKC λ) activity was also augmented in small-t-antigen-expressing 3T3-L1 adipocytes. Consistent with this result, both basal and insulin-stimulated glucose uptake were enhanced in these cells. In support of this result, when inhibitory anti-PP2A antibody was microinjected into 3T3-L1 adipocytes, we found a twofold increase in GLUT4 translocation in the absence of insulin. The small-t-antigen-induced increase in Akt and PKC λ activities was not inhibited by wortmannin, while the ability of small t antigen to enhance glucose transport was inhibited by dominant negative Akt (DN-Akt) expression and Akt small interfering RNA (siRNA) but not by DN-PKC λ expression or PKC λ siRNA. We conclude that PP2A is a negative regulator of insulin's metabolic signaling pathway by promoting dephosphorylation and inactivation of Akt and PKC λ and that most of the effects of PP2A to inhibit glucose transport are mediated through Akt.

scholarly journals Inactivation of p42 MAP kinase by protein phosphatase 2A and a protein tyrosine phosphatase, but not CL100, in various cell lines

1995 ◽  
Vol 5 (3) ◽  
pp. 283-295 ◽  
Author(s):  
Dario R. Alessi ◽  
Nestor Gomez ◽  
Greg Moorhead ◽  
Tom Lewis ◽  
Stephen M. Keyse ◽  
...  
Keyword(s):  
Map Kinase ◽  
Cell Lines ◽  
Protein Tyrosine Phosphatase ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine ◽  
Phosphatase 2A
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