Protein phosphatase 2A: variety of forms and diversity of functions.

Lechward, Katarzyna; Awotunde, Olubunmi S.; Światek, Wojciech; Muszyńska, Grażyna

doi:10.18388/abp.2001_3858

Cited by 182 publications

(92 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Rac1-mediated activation of PAK1 triggers a signalling pathway comprising p38 mitogen-activated kinase (p38MAPK) (Zhang et al, 1995). p38MAPK can be inactivated by the ubiquitous serine/threonine phosphatase PP2A (Sundaresan and Farndale, 2002), which resides in the nucleus and cytoplasm as well as at the plasma membrane (Lechward et al, 2001). In addition, PP2A can associate with and dephosphorylate PAK kinases (Westphal et al, 1999;Zhan et al, 2003), suggesting that PP2A represents a 'brake' on the Rac1-PAK-p38 MAPK pathway.…”

Section: Introductionmentioning

confidence: 99%

Rac1-induced cell migration requires membrane recruitment of the nuclear oncogene SET

Klooster

Leeuwen

Scheres

et al. 2007

EMBO J

121

115

View full text Add to dashboard Cite

The Rho GTPase Rac1 controls cell adhesion and motility. The effector loop of Rac1 mediates interactions with downstream effectors, whereas its C-terminus binds the exchange factor b-Pix, which mediates Rac1 targeting and activation. Here, we report that Rac1, through its C-terminus, also binds the nuclear oncogene SET/I2PP2A, an inhibitor of the serine/threonine phosphatase PP2A. We found that SET translocates to the plasma membrane in cells that express active Rac1 as well as in migrating cells. Membrane targeting of SET stimulates cell migration in a Rac1-dependent manner. Conversely, reduction of SET expression inhibits Rac1-induced migration, indicating that efficient Rac1 signalling requires membrane recruitment of SET. The recruitment of the SET oncogene to the plasma membrane represents a new feature of Rac1 signalling. Our results suggest a model in which Rac1-stimulated cell motility requires both effector loop-based downstream signalling and recruitment of a signalling amplifier, that is, SET, through the hypervariable C-terminus.

show abstract

Section: Introductionmentioning

confidence: 99%

Rac1-induced cell migration requires membrane recruitment of the nuclear oncogene SET

Klooster

Leeuwen

Scheres

et al. 2007

EMBO J

121

115

View full text Add to dashboard Cite

show abstract

“…Aa and Ca isoforms are considerably more abundant than Ab and Cb. The variable regulatory subunits are classified into four families of unrelated proteins: B (PR55), B 0 (B56 or PR61), B 00 (PR72), and B 000 (PR93/PR110), with at least 16 members in each of these subfamilies (Janssens and Goris, 2001;Lechward et al, 2001). The diverse composition of the PP2A holoenzyme provides many possibilities for cellular regulation.…”

mentioning

confidence: 99%

Generation of Ppp2Ca and Ppp2Cb conditional null alleles in mouse

Yi-jie

et al. 2011

Genesis

View full text Add to dashboard Cite

Protein phosphatase 2A (PP2A) is one of the most abundant serine/threonine phosphatases, with a critical role in embryonic development and human disease. There are two isoforms of the catalytic subunit of PP2A, Ppp2ca and Ppp2cb. Null mutation of Ppp2ca leads to early embryonic lethality at E6.5, hindering functional study of PP2A beyond this stage. We generated conditional null alleles of Ppp2ca and Ppp2cb by flanking with loxP sites exons 3 to 5 of Ppp2ca and exon 3 of Ppp2cb. Ppp2ca(fl/fl) mice did not display any visible phenotype. Homozygous mutants in which Cre-mediated excision resulted in global deletion of Ppp2ca displayed embryonic lethality and developmental defects similar to those previously reported. Ppp2cb(Δ/Δ) mice generated by the same strategy did not display any obvious morphological or physiological defects. These mouse strains can serve as important genetic tools to study the roles of PP2A during development and disease in a spatial- or temporal-specific manner.

show abstract

“…Mainly, the RING, B-box1 and B-box2 domains function synergistically to catalyze the ubiquitination of the catalytic subunit of PP2A (PP2Ac), its regulatory subunit alpha4 and the fused (Fu) kinase [1,[11][12][13]. PP2A is an essential mammalian serine/threonine phosphatase that regulates, among many, metabolism, cell-cycle progression and cell death [14][15][16][17]. Mammalian alpha4 protein is shown to down-regulate PP2Ac in the target of rapamycin (TOR) pathway [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Structural and functional observations of the P151L MID1 mutation reveal alpha4 plays a significant role in X‐linked Opitz Syndrome

Wright

Massiah

2017

The FEBS Journal

View full text Add to dashboard Cite

Mutations of human MID1 are associated with X-linked Opitz G Syndrome (XLOS), which is characterized by midline birth defects. XLOS-observed mutations within the MID1 B-box1 domain are associated with cleft lip/palate, wide-spaced eyes and hyperspadias. Three of the four XLOS-observed mutations in the B-box1 domain results in unfolding but the structural and functional effects of the P151L mutation is not characterized. Here, we demonstrate that the P151L mutation does not disrupt the overall tertiary structure of the B-box1 domain and the adjacent domains. In fact, MID1 E3 ligase activity is slightly enhanced. However, the P151L mutation disrupted the ability of MID1 to catalyze the poly-ubiquitination of alpha4, a novel regulator of PP2A. This observation is consistent with results observed with the other three structure-destabilizing B-box1 mutations in targeting alpha4 but not PP2A. Alpha4 is shown to bind and sequester the catalytic subunit of PP2A and protect it from MID1-mediated ubiquitination and as a result, an increase in alpha4 can contribute to an increase in PP2A, playing a greater role in midline development during embryogenesis.

show abstract

Protein phosphatase 2A: variety of forms and diversity of functions.

Cited by 182 publications

References 63 publications

Rac1-induced cell migration requires membrane recruitment of the nuclear oncogene SET

Rac1-induced cell migration requires membrane recruitment of the nuclear oncogene SET

Generation of Ppp2Ca and Ppp2Cb conditional null alleles in mouse

Structural and functional observations of the P151L MID1 mutation reveal alpha4 plays a significant role in X‐linked Opitz Syndrome

Contact Info

Product

Resources

About