Serine/threonine protein phosphatases in the control of cell function

DePaoli‐Roach, Anna A.; Park, In Kyung; Čeřovský, Václav; Csortos, Csilla; Durbin, Stephen D.; Kuntz, Martha J.; Sitikov, Albert; Tang, Pauline M.; Verin, Alexander D.; Zołnierowicz, Stanisław

doi:10.1016/0065-2571(94)90017-5

Cited by 134 publications

(125 citation statements)

References 73 publications

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“…When compared to PLB, GM is a large protein of 1122 amino acids and it is established that its Nterminal stretch is responsible for the binding of the catalytic subunit PP1C [32,33]. A previous hydropathy analysis of the amino acid sequence of GM had revealed a hydrophobic region likely to anchor the protein to the membrane of the SR [12]. Therefore to further understand what structural features could be involved in the interaction between GM and PLB, an additional sequence analysis was performed on GM.…”

Section: Discussionmentioning

confidence: 99%

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Biophysical interaction between phospholamban and protein phosphatase 1 regulatory subunit GM

Berrebi-Bertrand¹,

Souchet²,

Camelin³

et al. 1998

FEBS Letters

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Regulation of the sarco(endo)plasmic reticulum Ca P+ -ATPase (SERCA 2a) depends on the phosphorylation state of phospholamban (PLB). When PLB is phosphorylated, its inhibitory effect towards SERCA 2a is relieved, leading to an enhanced myocardial performance. This process is reversed by a sarcoplasmic reticulum (SR)-associated type 1 protein phosphatase (PP1) composed of a catalytic subunit PP1C and a regulatory subunit GM. Human GM and PLB have been produced in an in vitro transcription/translation system and used for co-immunoprecipitation and biosensor experiments. The detected interaction between the two partners suggests that cardiac PP1 is targeted to PLB via GM and we believe that this process occurs with the identified transmembrane domains of the two proteins. Thus, the interaction between PLB and GM may represent a specific way to modulate the SR function in human cardiac muscle.z 1998 Federation of European Biochemical Societies.

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Section: Discussionmentioning

confidence: 99%

“…Although GM, a 1122-residue protein, binds directly to glycogen, the mechanism by which it interacts with SR membranes is still unknown. It has been suggested that it could be due to a membrane-associated domain or a domain for interaction with a protein that binds to SR membranes [10,12,13].…”

Section: Introductionmentioning

confidence: 99%

Biophysical interaction between phospholamban and protein phosphatase 1 regulatory subunit GM

Berrebi-Bertrand¹,

Souchet²,

Camelin³

et al. 1998

FEBS Letters

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“…Previous studies have implicated serine\threonine protein phosphatase-2A (PP-2A) in a wide variety of cellular functions, including cellular metabolism, transcription and translation, ion transport, development, cell growth and differentiation [1][2][3][4]. The activity of an enzyme participating in so many diverse cellular processes must be tightly regulated in i o.…”

Section: Introductionmentioning

confidence: 99%

“…Little is known however, about the mechanism of regulation of PP-2A in i o. The PP-2A holoenzyme is a heterotrimer composed of catalytic (C), structural (A) and regulatory (B) subunits [1][2][3][4]. So far, over 15 regulatory subunits have been identified for PP-2A, which, in addition to regulating enzymic activity, are predicted to be involved in the subcellular targeting of the holoenzyme.…”

Section: Introductionmentioning

confidence: 99%

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

Begum

Ragolia

1999

Biochemical Journal

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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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“…Even though all of the B-subunits associate with the same dimeric C2⅐A core, no obvious homology has been found among the B, BЈ, and BЉ forms. The abundance of the diverse B-subunit isoforms and their association with the relatively invariant set of C2 and A subunits has led to the suggestion that the B-subunits are responsible for targeting specific phosphatase 2A holoenzymes to distinct cellular locales and/or for conferring specificity toward appropriate substrates (4,5,28).…”

mentioning

confidence: 99%

Saccharomyces cerevisiae Homologs of Mammalian B and B′ Subunits of Protein Phosphatase 2A Direct the Enzyme to Distinct Cellular Functions

Zhao

Boguslawski

Zitomer

et al. 1997

Journal of Biological Chemistry

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Protein phosphatase 2A (PP2A) is a major cellular serine/threonine protein phosphatase, present in the cell in a variety of heterotrimeric forms that differ in their associated regulatory B-subunit. Cloning of the mammalian B subunit has allowed the identification of a highly homologous Saccharomyces cerevisiae gene, RTS1. Disruption of the gene results in a temperaturesensitive growth defect that can be suppressed by expression of rabbit B ␣ or B ␥ isoforms. The B ␣ subunit is much more effective in restoring normal growth at 37°C than B ␥. Immunoprecipitated Rts1p was found associated with type 2A-specific protein phosphatase activity that is sensitive to 2 nM okadaic acid, but not to 100 nM phosphatase inhibitor-2, and to be phosphorylated in vivo. However, overexpression of RTS1 was unable to suppress the cold sensitivity, defective cytokinesis, and abnormal cell morphology resulting from defects in the CDC55 gene, which encodes the yeast homolog of a different B subunit of another form of 2A phosphatase, PP2A 1 . These results indicate that Rts1p is a yeast homolog of the mammalian B subunit and that the various regulatory B-subunits of PP2A are not functionally redundant but direct the enzyme to distinct cellular functions.

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Serine/threonine protein phosphatases in the control of cell function

Cited by 134 publications

References 73 publications

Biophysical interaction between phospholamban and protein phosphatase 1 regulatory subunit GM

Biophysical interaction between phospholamban and protein phosphatase 1 regulatory subunit GM

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

Saccharomyces cerevisiae Homologs of Mammalian B and B′ Subunits of Protein Phosphatase 2A Direct the Enzyme to Distinct Cellular Functions

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