Purification and Characterization of Two Putative HLA Class II Associated Proteins: PHAPI and PHAPII

Vaesen, Mark; Barnikol-Watanabe, Shitsu; Götz, H.; Awni, Lewa Adil; Cole, T.; Zimmermann, Bodo; Kratzin, Hartmut; Hilschmann, Norbert

doi:10.1515/bchm3.1994.375.2.113

Cited by 91 publications

(110 citation statements)

References 36 publications

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“…The structural feature of I 1 PP2A is characterized by four leucine-rich repeats (including the first 25-amino acid subtype-specific N-terminal region), a putative nuclear localization signal, and a long stretch of acidic amino acids at C-terminal ends (18,22). To define the binding domain as well as PP2A inhibition activity, the full-length I 1 PP2A protein and, based on its structure, a series of deletion mutants I 1 PP2A ⌬C1, I 1 PP2A ⌬C2, I 1 PP2A ⌬C3, I 1 PP2A ⌬C4, I 1 PP2A F2, I 1 PP2A F2-4, and I 1 PP2A F5 were generated (Fig.…”

Section: Domains Of I 1 Pp2a Involved In Its Binding To Pp2a Catalytimentioning

confidence: 99%

I PP2A 1 Affects Tau Phosphorylation via Association with the Catalytic Subunit of Protein Phosphatase 2A

Chen

Grundke‐Iqbal

et al. 2008

Journal of Biological Chemistry

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In Alzheimer disease (AD) brain, the level of I 1 PP2A, a 249-amino acid long endogenous inhibitor of protein phosphatase 2A (PP2A), is increased, the activity of the phosphatase is decreased, and the microtubule-associated protein Tau is abnormally hyperphosphorylated. However, little is known about the detailed regulatory mechanism by which PP2A activity is inhibited by I 1 PP2A and the consequent events in mammalian cells. In this study, we found that both I 1 PP2A and its N-terminal half I 1 PP2A(1-120), but neither I 1 PP2A(1-163) nor I 1 PP2A(164 -249) , inhibited PP2A activity in vitro, suggesting an autoinhibition by amino acid residues 121-163 and its neutralization by the C-terminal region. Furthermore, transfection of NIH3T3 cells produced a dose-dependent inhibition of PP2A activity by I 1 PP2A . I 1 PP2A and PP2A were found to colocalize in PC12 cells. I 1 PP2A could only interact with the catalytic subunit of PP2A (PP2Ac) and had no interaction with the regulatory subunits of PP2A (PP2A-A or PP2A-B) using a glutathione S-transferase-pulldown assay. The interaction was further confirmed by coimmunoprecipitation of I 1 PP2A and PP2Ac from lysates of transiently transfected NIH3T3 cells. The N-terminal isotype specific region of I 1 PP2A was required for its association with PP2Ac as well as PP2A inhibition. In addition, the phosphorylation of Tau was significantly increased in PC12/Tau441 cells transiently transfected with full-length I 1 PP2A and with PP2Ac-interacting I 1 PP2A deletion mutant 1-120 (I 1 PP2A ⌬C2). Double immunofluorescence staining showed that I 1 PP2A and I 1 PP2A ⌬C2 increased Tau phosphorylation and impaired the microtubule network and neurite outgrowth in PC12 cells treated with nerve growth factor.

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Section: Domains Of I 1 Pp2a Involved In Its Binding To Pp2a Catalytimentioning

confidence: 99%

I PP2A 1 Affects Tau Phosphorylation via Association with the Catalytic Subunit of Protein Phosphatase 2A

Chen

Grundke‐Iqbal

et al. 2008

Journal of Biological Chemistry

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“…21 Vitamin D 3 stimulates monocytic differentiation in U937 cells via vitamin D 3 receptordependent expression of surface markers CD11b and CD14. 23 To determine whether overexpression of SET mimics other cellular responses to vitamin D 3 …”

Section: Set and Vitamin D 3 Stimulate The Expression Of Different Mamentioning

confidence: 99%

“…One-third of its C-terminal acidic amino acids form an acidic tail. [2][3][4] SET (also known as template-activating factor I beta (TAF-Ib)) physically interacts with several protein complexes, which suggests that it has diverse functions including Granzyme A-induced apoptosis, 5,6 chromosome remodeling, 7 transcriptional regulation, 8 mRNA stabilization 9 and cell cycle regulation. [10][11][12][13] SET also forms a complex with the MLL leukemic fusion protein and type-2A protein phosphatase (PP2A).…”

Section: Introductionmentioning

confidence: 99%

SET-induced calcium signaling and MAPK/ERK pathway activation mediate dendritic cell-like differentiation of U937 cells

Kandilci

Grosveld

2005

Leukemia

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Human SET, a target of chromosomal translocation in human leukemia encodes a highly conserved, ubiquitously expressed, nuclear phosphoprotein. SET mediates many functions including chromatin remodeling, transcription, apoptosis and cell cycle control. We report that overexpression of SET directs differentiation of the human promonocytic cell line U937 along the dendritic cell (DC) pathway, as cells display typical morphologic changes associated with DC fate and express the DC surface markers CD11b and CD86. Differentiation occurs via a calcium-dependent mechanism involving the CaMKII and MAPK/ERK pathways. Similar responses are elicited by interferon-c (IFN-c) treatment with the distinction that IFN-c signaling activates the DNA-binding activity of STAT1 whereas SET overexpression does not. In addition, unlike IFN-c signaling, SET generated stress-induced p38/MAPK activity. Interestingly, IFN-c treatment transiently upregulated endogenous SET in a dose-dependent manner. These results suggest that SET is part of both IFN-c-mediated and stress-mediated cellular responses and that SET induces cell differentiation via calcium and MAPK/ ERK pathways.

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“…PHAPI, first purified by affinity with an agarose-conjugated synthetic cytoplasmic region of HLA-DR ␣ chain, is a putative HLA class II-associated cytosolic protein (9), later identified as a phosphoprotein (10). It belongs to a group of proteins containing 20 -29-residue leucine-rich repeat motifs.…”

mentioning

confidence: 99%

Protein Phosphatase 2A, a Negative Regulator of the ERK Signaling Pathway, Is Activated by Tyrosine Phosphorylation of Putative HLA Class II-associated Protein I (PHAPI)/pp32 in Response to the Antiproliferative Lectin, Jacalin

Yu¹,

Packman

Weldon

et al. 2004

Journal of Biological Chemistry

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Protein phosphatase 2A (PP2A) is a family of mammalian serine/threonine phosphatases that is involved in the control of many cellular functions including those mediated by extracellular signal-regulated kinase (ERK) signaling. While investigating the reversible antiproliferative effect of the dietary lectin, jacalin, which binds the Thomsen-Friedenreich antigen (galactose ␤1-3 N-acetylgalactosamine ␣-), we have found that this lectin (30 g/ml) induces rapid, transient, tyrosine phosphorylation of putative human HLA-DR-associated protein I (PHAPI, also known as the tumor suppressor pp32) in HT29 human colon cancer cells. This is accompanied by the release of PP2A from association with PHAPI, allowing increased phosphatase activity of PP2A (by 42 ؎ 10% at 10 min) and consequent complete dephosphorylation of the ERK kinase, MEK1/2, by 10 min and of ERK1/2 by 60 min. PHAPI knockdown by RNA interference abolished the effects of jacalin on PP2A activation and MEK inhibition. Thus phosphorylation of PHAPI/pp32 is a critical regulatory step in PP2A activation and ERK signaling.Protein phosphatase 2A (PP2A) 1 is a family of mammalian serine/threonine phosphatases that accounts for the major portion of serine/threonine kinase activity in most cells. PP2A is a trimeric holoenzyme complex and is composed of a catalytic C subunit, a structural A subunit, and a regulatory B-type subunit, each encoded by separate genes (1, 2). Up to 75 different trimeric ABC holoenzymes may exist. The C subunit is the enzymatically active component, A is a scaffolding component, and B acts as a targeting module that directs the enzyme to various intracellular locations and also provides substrate specificity.PP2A was initially thought to act passively and nonspecifically in antagonizing the action of kinases by removal of phosphate groups from their substrates, but it has become clear that it is tightly regulated by mechanisms that include variation in its subunit composition (3), phosphorylation, and/or methylation of its catalytic subunit and signal-regulated targeting to specific subcellular compartments (1-4). PP2A is an important negative regulator of the extracellular signal-regulated kinase (ERK) signaling pathway (5-7) and is involved in the control of many cellular functions including metabolism, transcription, translation, RNA splicing, DNA replication, cell cycle progression, transformation, and apoptosis (1-8).PHAPI, first purified by affinity with an agarose-conjugated synthetic cytoplasmic region of HLA-DR ␣ chain, is a putative HLA class II-associated cytosolic protein (9), later identified as a phosphoprotein (10). It belongs to a group of proteins containing 20 -29-residue leucine-rich repeat motifs. The principal function of these motifs seems to be the provision of a structural framework that allows protein-protein interactions (11). PHAPI is also known as pp32, a potent tumor suppressor (12-15) that is down-regulated in cancer with reciprocal increased expression of pp32r1 and pp32r2, other members of the pp32 gene family (...

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Purification and Characterization of Two Putative HLA Class II Associated Proteins: PHAPI and PHAPII

Cited by 91 publications

References 36 publications

I PP2A 1 Affects Tau Phosphorylation via Association with the Catalytic Subunit of Protein Phosphatase 2A

I PP2A 1 Affects Tau Phosphorylation via Association with the Catalytic Subunit of Protein Phosphatase 2A

SET-induced calcium signaling and MAPK/ERK pathway activation mediate dendritic cell-like differentiation of U937 cells

Protein Phosphatase 2A, a Negative Regulator of the ERK Signaling Pathway, Is Activated by Tyrosine Phosphorylation of Putative HLA Class II-associated Protein I (PHAPI)/pp32 in Response to the Antiproliferative Lectin, Jacalin

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