Mutation of Tyr307 and Leu309 in the Protein Phosphatase 2A Catalytic Subunit Favors Association with the α4 Subunit Which Promotes Dephosphorylation of Elongation Factor-2†

Biochemistry ◽  
1999 ◽  
Vol 38 (32) ◽  
pp. 10371-10376 ◽  
Author(s):  
Heekyoung Chung ◽  
Angus C. Nairn ◽  
Kohei Murata ◽  
David L. Brautigan
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Elongation Factor ◽  
Catalytic Subunit ◽  
Elongation Factor 2 ◽  
Phosphatase 2A

scholarly journals Activity of protein phosphatases against initiation factor-2 and elongation factor-2

1990 ◽  
Vol 272 (1) ◽  
pp. 175-180 ◽  
Author(s):  
N T Redpath ◽  
C G Proud
Keyword(s):  
Phosphatase Activity ◽  
Protein Phosphatase ◽  
Protein Phosphatases ◽  
Protein Phosphatase 2A ◽  
Elongation Factor ◽  
Protein Phosphatase 1 ◽  
Initiation Factor ◽  
Elongation Factor 2 ◽  
Initiation Factor 2 ◽  
Phosphatase 2A

The protein phosphatases active against phosphorylase a, elongation factor-2 (EF-2) and the alpha-subunit of initiation factor-2 (eIF-2) [eIF-2(alpha P)] were studied in extracts of rabbit reticulocytes. Swiss-mouse 3T3 fibroblasts and rat hepatocytes, by use of the specific phosphatase inhibitors okadaic acid and inhibitor proteins-1 and -2. In all three extracts tested, both phosphatase-1 and phosphatase-2A contributed to overall phosphatase activity against phosphorylase and eIF-2(alpha P), but phosphatase-2B and -2C did not. In contrast, only protein phosphatase-2A was active against EF-2. Furthermore, in hepatocytes there was substantial type-2C phosphatase activity against EF-2, but not against phosphorylase or eIF-2 alpha. These findings in cell extracts were borne out by data obtained by studying the activities of purified protein phosphatase-1 and -2A against eIF-2(alpha P) and eIF-2(alpha P) was a moderately good substrate for both enzymes (relative to phosphorylase a). In contrast, EF-2 was a very poor substrate for protein phosphatase-1, but was dephosphorylated faster than phosphorylase a by protein phosphatase-2A. The implications of these findings for the control of translation and their relationships to previous work are discussed.

scholarly journals The catalytic subunit of protein phosphatase 2A is carboxyl-methylated in vivo.

1994 ◽  
Vol 269 (23) ◽  
pp. 16311-16317 ◽  
Author(s):  
B. Favre ◽  
S. Zolnierowicz ◽  
P. Turowski ◽  
B.A. Hemmings
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Catalytic Subunit ◽  
Phosphatase 2A

Structure and transcriptional regulation of protein phosphatase 2A catalytic subunit genes [Erratum to document cited in CA114(3):18572v]

Biochemistry ◽  
1991 ◽  
Vol 30 (21) ◽  
pp. 5328-5328 ◽  
Author(s):  
Yeesim Khew-Goodall ◽  
Regina E. Mayer ◽  
Francisca Maurer ◽  
Stuart R. Stone ◽  
Brian A. Hemmings
Keyword(s):  
Transcriptional Regulation ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Catalytic Subunit ◽  
Phosphatase 2A

Identification of protein phosphatase 2A as an interacting protein of leucine-rich repeat kinase 2

2016 ◽  
Vol 397 (6) ◽  
pp. 541-554 ◽  
Author(s):  
Panagiotis S. Athanasopoulos ◽  
Wright Jacob ◽  
Sebastian Neumann ◽  
Miriam Kutsch ◽  
Dirk Wolters ◽  
...  
Keyword(s):  
Hela Cells ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Catalytic Subunit ◽  
Sodium Selenate ◽  
Leucine Rich Repeat ◽  
Human Neuroblastoma ◽  
Interacting Protein ◽  
Cellular Degeneration ◽  
Phosphatase 2A

Abstract Mutations in the gene coding for the multi-domain protein leucine-rich repeat kinase 2 (LRRK2) are the leading cause of genetically inherited Parkinson’s disease (PD). Two of the common found mutations are the R1441C and G2019S. In this study we identified protein phosphatase 2A (PP2A) as an interacting partner of LRRK2. We were able to demonstrate that the Ras of complex protein (ROC) domain is sufficient to interact with the three subunits of PP2A in human neuroblastoma SH-SY5Y cells and in HeLa cells. The alpha subunit of PP2A is interacting with LRRK2 in the perinuclear region of HeLa cells. Silencing the catalytic subunit of PP2A by shRNA aggravated cellular degeneration induced by the pathogenic R1441C-LRRK2 mutant expressed in neuroblastoma SH-SY5Y cells. A similar enhancement of apoptotic nuclei was observed by downregulation of the catalytic subunit of PP2A in cultured cortical cells derived from neurons overexpressing the pathogenic mutant G2019S-LRRK2. Conversely, pharmacological activation of PP2A by sodium selenate showed a partial neuroprotection from R1441C-LRRK2-induced cellular degeneration. All these data suggest that PP2A is a new interacting partner of LRRK2 and reveal the importance of PP2A as a potential therapeutic target in PD.

scholarly journals A Novel Interaction of the Catalytic Subunit of Protein Phosphatase 2A with the Adaptor Protein CIN85 Suppresses Phosphatase Activity and Facilitates Platelet Outside-in αIIbβ3 Integrin Signaling

2016 ◽  
Vol 291 (33) ◽  
pp. 17360-17368 ◽  
Author(s):  
Tanvir Khatlani ◽  
Subhashree Pradhan ◽  
Qi Da ◽  
Tanner Shaw ◽  
Vladimir L. Buchman ◽  
...  
Keyword(s):  
Phosphatase Activity ◽  
Protein Interactions ◽  
Protein Phosphatase ◽  
Thrombus Formation ◽  
Protein Phosphatase 2A ◽  
Adaptor Protein ◽  
Fibrin Clot ◽  
Catalytic Subunit ◽  
Clot Retraction ◽  
Phosphatase 2A

The transduction of signals generated by protein kinases and phosphatases are critical for the ability of integrin αIIbβ3 to support stable platelet adhesion and thrombus formation. Unlike kinases, it remains unclear how serine/threonine phosphatases engage the signaling networks that are initiated following integrin ligation. Because protein-protein interactions form the backbone of signal transduction, we searched for proteins that interact with the catalytic subunit of protein phosphatase 2A (PP2Ac). In a yeast two-hybrid study, we identified a novel interaction between PP2Ac and an adaptor protein CIN85 (Cbl-interacting protein of 85 kDa). Truncation and alanine mutagenesis studies revealed that PP2Ac binds to the P3 block (396PAIPPKKPRP405) of the proline-rich region in CIN85. The interaction of purified PP2Ac with CIN85 suppressed phosphatase activity. Human embryonal kidney 293 αIIbβ3 cells overexpressing a CIN85 P3 mutant, which cannot support PP2Ac binding, displayed decreased adhesion to immobilized fibrinogen. Platelets contain the ∼85 kDa CIN85 protein along with the PP2Ac-CIN85 complex. A myristylated cell-permeable peptide derived from residues 395–407 of CIN85 protein (P3 peptide) disrupted the platelet PP2Ac-CIN85 complex and decreased αIIbβ3 signaling dependent functions such as platelet spreading on fibrinogen and thrombin-mediated fibrin clot retraction. In a phospho-profiling study P3 peptide treated platelets also displayed decreased phosphorylation of several signaling proteins including Src and GSK3β. Taken together, these data support a role for the novel PP2Ac-CIN85 complex in supporting integrin-dependent platelet function by dampening the phosphatase activity.

Regulation by glucose and calcium of the carboxylmethylation of the catalytic subunit of protein phosphatase 2A in insulin-secreting INS-1 cells

2004 ◽  
Vol 286 (6) ◽  
pp. E1032-E1041 ◽  
Author(s):  
Rengasamy Palanivel ◽  
Rajakrishnan Veluthakal ◽  
Anjaneyulu Kowluru
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Catalytic Subunit ◽  
Inhibitory Effects ◽  
Β Cells ◽  
Intact Cells ◽  
Phosphatase 2A ◽  
Glucose Metabolites

Previously, we reported that the catalytic subunit of protein phosphatase 2A (PP2Ac) undergoes carboxylmethylation (CML) at its COOH-terminal leucine, and that inhibitors of such a posttranslational modification markedly attenuate nutrient-induced insulin secretion from isolated β-cells. More recent studies have suggested direct inhibitory effects of glucose metabolites on PP2A activity in isolated β-cells, implying that inhibition of PP2A leads to stimulation of insulin secretion. Because the CML of PP2Ac has been shown to facilitate the holoenzyme assembly and subsequent functional activation of PP2A, we investigated putative regulation by glucose of the CML of PP2Ac in insulin-secreting (INS)-1 cells. Our data indicated a marked inhibition by specific intermediates of glucose metabolism (e.g., citrate and phospho enolpyruvate) of the CML of PP2Ac in INS-1 cell lysates. Such inhibitory effects were also demonstrable in intact cells by glucose. Mannoheptulose, an inhibitor of glucose metabolism, completely prevented inhibitory effects of glucose on the CML of PP2Ac. Moreover, glucose-mediated inhibition of the CML of PP2Ac was resistant to diazoxide, suggesting that glucose metabolism and the generation of glucose metabolites might control inhibition of the CML of PP2Ac. A membrane-depolarizing concentration of KCl also induced inhibition of the CML of PP2Ac in intact INS cells. On the basis of these data, we propose that glucose metabolism and increase in intracellular calcium facilitate inhibition of the CML of PP2Ac, resulting in functional inactivation of PP2A. This, in turn, might retain the key signaling proteins of the insulin exocytotic cascade in their phosphorylated state, leading to stimulated insulin secretion.

scholarly journals Structural basis for PTPA interaction with the invariant C-terminal tail of PP2A

2014 ◽  
Vol 395 (7-8) ◽  
pp. 881-889 ◽  
Author(s):  
Christian Löw ◽  
Esben M. Quistgaard ◽  
Michael Kovermann ◽  
Madhanagopal Anandapadamanaban ◽  
Jochen Balbach ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Posttranslational Modifications ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Catalytic Subunit ◽  
Structural Basis ◽  
Interaction Site ◽  
Interaction Partners ◽  
Phosphatase 2A ◽  
Additional Interaction

Abstract Protein phosphatase 2A (PP2A) is a highly abundant heterotrimeric Ser/Thr phosphatase involved in the regulation of a variety of signaling pathways. The PP2A phosphatase activator (PTPA) is an ATP-dependent activation chaperone, which plays a key role in the biogenesis of active PP2A. The C-terminal tail of the catalytic subunit of PP2A is highly conserved and can undergo a number of posttranslational modifications that serve to regulate the function of PP2A. Here we have studied structurally the interaction of PTPA with the conserved C-terminal tail of the catalytic subunit carrying different posttranslational modifications. We have identified an additional interaction site for the invariant C-terminal tail of the catalytic subunit on PTPA, which can be modulated via posttranslational modifications. We show that phosphorylation of Tyr307PP2A-C or carboxymethylation of Leu309PP2A-C abrogates or diminishes binding of the C-terminal tail, whereas phosphorylation of Thr304PP2A-C is of no consequence. We suggest that the invariant C-terminal residues of the catalytic subunit can act as affinity enhancer for different PP2A interaction partners, including PTPA, and a different ‘code’ of posttranslational modifications can favour interactions to one subunit over others.

scholarly journals VIP1, a bZIP protein, interacts with the catalytic subunit of protein phosphatase 2A in Arabidopsis thaliana

2019 ◽  
Vol 15 (2) ◽  
pp. 1706026 ◽  
Author(s):  
Hyuk Sung Yoon ◽  
Kaien Fujino ◽  
Shenkui Liu ◽  
Tetsuo Takano ◽  
Daisuke Tsugama
Keyword(s):  
Arabidopsis Thaliana ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Catalytic Subunit ◽  
Bzip Protein ◽  
Phosphatase 2A
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