Regulation of Protein Phosphatase 2A by Direct Interaction with Casein Kinase 2α

Hériché, Jean‐Karim; Lebrin, Franck; Rabilloud, Thierry; Leroy, Didier; Chambaz, E.M.; Goldberg, Yves

doi:10.1126/science.276.5314.952

Cited by 264 publications

(223 citation statements)

References 25 publications

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“…Our observations coincide with a number of recent studies documenting PP-2A association with different kinases [12][13][14][15][16][17][18][19][20][21][22]. For example, studies by Heriche et al [12] indicate that casein kinase 2α associates with PP-2A and causes activation of PP-2A.…”

Section: Discussionsupporting

confidence: 92%

“…For example, studies by Heriche et al [12] indicate that casein kinase 2α associates with PP-2A and causes activation of PP-2A. A recent study by Westphal et al [43] indicates that PP-2A forms complexes with p70 S6 kinase, p21-activated kinase-1 (PAK-1) and p21-activated kinase-3 (PAK-3) in i o.…”

Section: Discussionmentioning

confidence: 99%

“…For example, PP-2A has been shown to bind the β2-adrenergic receptor [11], casein kinase 2α [12], homeobox gene 11 [13], tau [14], translation termination eukaryotic release factor 1 [15], adenovirus e4orf4 protein [16], α4 protein [17], neurofilament proteins [18,19] and small t and middle t antigens encoded by DNA tumour viruses [20,21]. Recent studies by Westphal et al [22] identified a calmodulin IV (CaMIV)-PP-2A complex in which PP-2A dephosphorylates…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Furthermore, it has been shown that PP2A can form complexes with CKII or a calciumcalmodulin-dependent kinase (Heriche et al 1997;Westphal et al 1998), suggesting that phosphorylation and dephosphorylation of cellular proteins are tightly coupled. Interestingly, both CKII and a calciumcalmodulin-dependent kinase were shown to be FRQ kinases in Neurospora (Yang et al 2001, raising the possibility that the functions of CKII and CAMK-1 in FRQ phosphorylation are regulated by PP2A.…”

Section: Genes and Development 257mentioning

confidence: 99%

Distinct roles for PP1 and PP2A in the Neurospora circadian clock

Yang¹,

He²,

Cheng³

et al. 2004

Genes Dev.

111

117

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Phosphorylation of the Neurospora circadian clock protein FREQUENCY by several kinases promotes its degradation and is important for the function of the circadian feedback loop. Here, we show that FRQ is less stable in a ppp-1 (catalytic subunit of PP1) mutant, resulting in its advanced phase and short period. In contrast, FRQ stability is not altered in a rgb-1 (a regulatory subunit of PP2A) mutant, but levels of frq protein and mRNA are low, resulting in a low-amplitude and longperiod oscillation of the clock. Furthermore, PP1 and PP2A expressed in Neurospora can dephosphorylate the endogenous FRQ in vitro, suggesting that these two phosphatases may differentially regulate FRQ and, consequently, the behavior of the circadian clock.Supplemental material is available at http://www.genesdev.org.Received September 15, 2003; revised version accepted December 15, 2003. Reversible phosphorylation is an important regulatory mechanism for many biological processes in eukaryotic organisms. The phosphorylation state of a protein is controlled dynamically by protein kinases and phosphatases. Previous studies have demonstrated that phosphorylation of circadian clock proteins is an essential posttranscriptional mechanism in the regulation of circadian clocks (Dunlap 1999;Young and Kay 2001). Several kinases, including casein kinase I (CKI) and CKII, have been shown to phosphorylate and regulate the key clock components in eukaryotic systems Sugano et al. 1999;Lowrey et al. 2000;Gorl et al. 2001;Yang et al. 2002).FREQUENCY (FRQ), WHITE COLLAR-1 (WC-1), and WC-2 proteins are three key components in the Neurospora frq-wc-based circadian oscillator . In addition to being the circadian blue light photoreceptor (Froehlich et al. 2002;He et al. 2002), in the dark, WC-1 forms a heterodimeric complex with WC-2 through their PAS domains and activate frq transcription by binding its promoter (Crosthwaite et al. 1997;Talora et al. 1999;Cheng et al. 2001bCheng et al. , 2002Cheng et al. , 2003Froehlich et al. 2003). FRQ, the negative element of the feedback loop, inhibits its own transcription through interactions with the WC complex (Aronson et al. 1994;Cheng et al. 2001a;Denault et al. 2001;Froehlich et al. 2003). FRQ protein is immediately phosphorylated after its synthesis and becomes extensively phosphorylated prior to its degradation by the ubiquitin/proteasome pathway Liu et al. 2000;He et al. 2003). In constant darkness, FRQ is not only robustly rhythmic in its cellular concentration, but also in its phosphorylation states, so that the level and the phosphorylation status of FRQ define the time of the clock during a circadian cycle .Phoshorylation of FRQ is mediated by CKI, CKII, and a calcium/calmodulin-dependent kinase (Gorl et al. 2001;Yang et al. 2001Yang et al. , 2002Yang et al. , 2003. Molecular, genetic, and biochemical experiments have shown that phosphorylation of FRQ has several functions. Mutations of the FRQ phosphorylation sites lead to the stabilization of the FRQ protein and long period rhythms of the clock (Li...

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“…The enzyme is described as a multi-subunit protein kinase that is generated by the association of two catalytic subunits a or a 0 with a dimer of b regulatory subunits leading to the idea that CK2 functions as a stable heterotetrameric complex. However, this traditional view has been challenged by the evidence for naturally occurring free monomeric CK2a (Dobrowolska et al, 1992;Stigare et al, 1993;Heriche et al, 1997) and for an unbalanced expression of CK2 subunits in different mammalian tissues (Stalter et al, 1994;Pinna and Meggio, 1997;Guerra et al, 1999b;Ghavidel and Schultz, 2001;Keller et al, 2001). Moreover, the marked elevation of CK2 enzymatic activity in various solid tumors is suspected to result in the suppression of cellular apoptosis, aiding tumor resistance to radiation and anticancer drug treatments (Guerra and Issinger, 1999;Ahmed et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

p53-dependent inhibition of mammalian cell survival by a genetically selected peptide aptamer that targets the regulatory subunit of protein kinase CK2

Martel

Filhol

Colas³

et al. 2006

Oncogene

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Regulation of Protein Phosphatase 2A by Direct Interaction with Casein Kinase 2α

Cited by 264 publications

References 25 publications

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

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

Distinct roles for PP1 and PP2A in the Neurospora circadian clock

p53-dependent inhibition of mammalian cell survival by a genetically selected peptide aptamer that targets the regulatory subunit of protein kinase CK2

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