Brain Actin-associated Protein Phosphatase 1 Holoenzymes Containing Spinophilin, Neurabin, and Selected Catalytic Subunit Isoforms

MacMillan, Leigh B.; Bass, Martha A.; Cheng, Nikki; Howard, Eric F.; Tamura, Masaaki; Strack, Stefan; Wadzinski, Brian E.; Colbran, Roger J.

doi:10.1074/jbc.274.50.35845

Cited by 98 publications

(114 citation statements)

References 40 publications

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“…Neurabin II belongs to this class of regulators because it negatively regulates the PP1 catalytic subunit activity. Native neurabin II associates with PP1 (44). DCX, neurabin II, and PP1 are found in the same protein complex when PP1 is pulled down with PP1-specific microcystin-agarose beads and also when DCX is immunoprecipitated from mouse brain extracts (31).…”

Section: Discussionmentioning

confidence: 96%

Ectopic Doublecortin Gene Expression Suppresses the Malignant Phenotype in Glioblastoma Cells

Santra¹,

Zhang²,

Santra³

et al. 2006

Cancer Research

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Doublecortin (DCX) is one of the three genes found from Affymetrix gene chip analysis related to glioma patient survival. Two other genes (e.g., osteonectin and semaphorin 3B) are well characterized as antioncogenic and tumor suppressor genes. However, there is no report about the involvement of DCX in cancer. Here, we show that gene transfer technology into DCX-deficient glioblastoma cell lines, such as A172, U87, U251N, RG2, and 9L, with DCX cDNA significantly suppressed growth of these glioma cells. U87 cells with ectopic expression of DCX exhibit a marked suppression of the transformed phenotype as growth arrested in the G 2 phase of the cell cycle progression, small colony formation in soft agar, and no tumor formation in nude rats. This transformed phenotype can be restored by knocking down DCX expression with DCX small interfering RNA. DCX was highly phosphorylated in glioma cells. Phosphorylation in the glioma cells was greater than in noncancer cells such as mouse NIH 3T3 and human embryonic kidney 293T cells. Coimmunoprecipitation of the phosphorylated DCX and spinophilin/neurabin II from DCX-synthesizing glioma cells indicated their interaction. This interaction would lead to a block of anchorage-independent growth as neurabin II is a synergistic inhibitor of anchorage-independent growth with p14ARF (ARF). Interaction between phosphorylated DCX and neurabin II may induce the association of the protein phosphatase 1 catalytic subunit (PP1) with neurabin II and inactivate PP1 and block mitosis during G 2 and M phases of the cell cycle progression. Thus, DCX seems to be a tumor suppressor of glioma. (Cancer Res 2006; 66(24): 11726-35)

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Section: Discussionmentioning

confidence: 96%

Ectopic Doublecortin Gene Expression Suppresses the Malignant Phenotype in Glioblastoma Cells

Santra¹,

Zhang²,

Santra³

et al. 2006

Cancer Research

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“…47 SPN selectively interacts with PPP1CC in the spinal cord, and it has been suggested that this binding is, at least in part, responsible for the enrichment of PPP1CC at synapses. 48 Similarly, the binding of SPN to PPP1CA results in partial coupled regulation between SPN and PP1a, as lower levels of SPN led to decreased PPP1CA Figure 4 (See opposite page). Loss of Spn increases p53 activity.…”

Section: Discussionmentioning

confidence: 98%

Spinophilin acts as a tumor suppressor by regulating Rb phosphorylation

Ferrer¹,

Blanco‐Aparicio²,

Peregrina³

et al. 2011

Cell Cycle

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“…Nuclear extract (5 g) was incubated in phosphatase buffer (20 mM Tris-HCl (pH 7.0), 1 mM DTT, 0.1 mM EGTA, 2 mM MgCl 2 , 1ϫ protease inhibitor mixture solution (Roche Molecular Biochemicals)) at 4 or 30°C for the indicated period of time. The MIN6 nuclear extract was incubated at 30°C in phosphatase buffer with CIAP (0.25 l/reaction (10-l reaction mixture volume); 20 units/l (Promega)) or BPP catalytic subunit mixture (1 l/reaction (10 l), 360 fmol/min using glycogen phosphorylase (31)). The brain protein phosphatase catalytic subunitenriched preparation was prepared by ethanol precipitation of a rat brain soluble extract (31).…”

Section: Methodsmentioning

confidence: 99%

The DNA Binding Activity of the RIPE3b1 Transcription Factor of Insulin Appears to Be Influenced by Tyrosine Phosphorylation

Matsuoka

Zhao

Stein

2001

Journal of Biological Chemistry

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The RIPE3b1 DNA binding factor plays a critical role in pancreatic islet ␤ cell-specific and glucose-regulated transcription of the insulin gene. Recently it was shown that RIPE3b1 binding activity in ␤ cell nuclear extracts is reduced by treatment with either calf intestinal alkaline phosphatase (CIAP) or a brain-enriched phosphatase preparation (BPP) (Zhao, L., Cissell, M. A., Henderson, E., Colbran, R., and Stein, R. (2000) J. Biol. Chem. 275, 10532-10537). Evidence is presented here suggesting that a tyrosine phosphatase(s) influences the ability of RIPE3b1 to bind to the insulin C1 element in ␤ cells. We found that RIPE3b1 binding was inhibited upon incubating ␤ cell nuclear extracts at 30°C. In contrast, PDX-1 and MLTF-1 transcription factor binding activity was unaffected under these conditions. The loss in RIPE3b1 binding activity was prevented by inhibitors of tyrosine phosphatases (sodium orthovanadate and sodium molybdate) but not by inhibitors of serine/threonine phosphatases (sodium fluoride, okadaic acid, and microcystin LR). CIAP-and BPP-catalyzed inhibition of RIPE3b1 binding was also blocked by these tyrosine phosphatase inhibitors. Collectively, the data suggested that removal of a tyrosine(s) within RIPE3b1 prevented activator binding to insulin C1 control element sequences. The presence of a key phosphorylated tyrosine(s) within this transcription factor was further supported by the ability of the 4G10 anti-phosphotyrosine monoclonal antibody to immunoprecipitate RIPE3b1 DNA binding activity. We discuss how tyrosine phosphorylation, a very rare and highly significant regulatory modification, may control RIPE3b1 activator function.Insulin is a polypeptide hormone that plays a critical role in glucose homeostasis by stimulating the uptake of glucose into cells. Expression of insulin in adults is limited to pancreatic islet ␤ cells primarily because of the recognition, by specific positive-acting transcription factors, of its enhancer region, which is located between nucleotides Ϫ340 and Ϫ91 relative to the insulin gene transcription start site (1-3). Selective activation from this region is predominantly mediated by the C2 (Ϫ317 to Ϫ311 base pairs) (2), A3 (Ϫ205 to Ϫ189 base pairs) (4 -6), C1 (Ϫ115 to Ϫ107 base pairs) (7-9), and E elements (Ϫ100 to Ϫ91 base pairs) (4, 7, 10). (These insulin cis-elements are labeled in accordance with the nomenclature proposed by German et al. (11).) The factors that act at A3, C1, and E also control glucose-inducible transcription (5,8,(12)(13)(14)(15), the primary metabolic regulator of insulin gene expression in vivo.The C2 (i.e. PAX6 (2)) and A3 (i.e. PDX-1 (6, 16, 17)) activators are islet ␤ cell-enriched homeodomain proteins, whereas a basic helix-loop-helix-containing protein controls E element stimulation (i.e. BETA2 (18)). Strikingly, these proteins regulate gene expression within islet cell types and during pancreogenesis. Thus, an inactivating mutation in the pdx-1 locus affects a very early development step that prevents both exocrine and endocrine p...

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Brain Actin-associated Protein Phosphatase 1 Holoenzymes Containing Spinophilin, Neurabin, and Selected Catalytic Subunit Isoforms

Cited by 98 publications

References 40 publications

Ectopic Doublecortin Gene Expression Suppresses the Malignant Phenotype in Glioblastoma Cells

Ectopic Doublecortin Gene Expression Suppresses the Malignant Phenotype in Glioblastoma Cells

Spinophilin acts as a tumor suppressor by regulating Rb phosphorylation

The DNA Binding Activity of the RIPE3b1 Transcription Factor of Insulin Appears to Be Influenced by Tyrosine Phosphorylation

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