Disease relevance of Ppp1r9b

• We used the rat carotid artery model of restenosis to demonstrate that adenovirus-mediated localized arterial transduction of RB2/p130 at the time of angioplasty significantly reduced neointimal hyperplasia and prevented restenosis [1].
• The retinoblastoma family members p107 and p130 were previously shown to be essential effectors of FGF-induced growth arrest in chondrocytes [2].
• The broad band of semi-purified p130 became sharp at an elevated position in the gel upon treatment with orthovanadate in vivo or with c-Src kinase produced using a baculovirus vector in vitro, whereas it shifted at a lower position upon treatment with alkaline phosphatase in vitro [3].
• The minimal promoter region of Rb2/p130 in T98G human glioblastoma cells was identified and its analysis revealed the presence of a KER1 palindromic sequence able to bind the transcription factor AP-2, a regulatory protein that plays a crucial role in ectodermal differentiation [4].
• We also found that rat PC12 pheochromocytoma cells, when induced to differentiate by NGF, displayed an increase of AP-2 protein levels and of Rb2/p130 transcription and protein levels [4].

High impact information on Ppp1r9b

• Here we show that p130 is the predominant Rb family member associated with E2F in neurons, that its major partner for repression of pro-apoptotic genes is E2F4, and that the p130-E2F4 complex recruits the chromatin modifiers HDAC1 and Suv39H1 to promote gene silencing and neuron survival [5].
• Protein phosphatase 1 modulation of neostriatal AMPA channels: regulation by DARPP-32 and spinophilin [6].
• We show that p130 plays an important role in signaling by the type A receptor for gamma-aminobutyric acid (GABA) [7].
• Among these proteins, a 125-135 kDa protein (p130) shows marked phosphorylation at tyrosines and tight association with v-Crk, suggesting a direct signal mediator of v-Crk [8].
• A novel signaling molecule, p130, forms stable complexes in vivo with v-Crk and v-Src in a tyrosine phosphorylation-dependent manner [8].

Chemical compound and disease context of Ppp1r9b

• Alterations of the retinoblastoma-related gene RB2/p130 in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats [9].

Biological context of Ppp1r9b

• Brain actin-associated protein phosphatase 1 holoenzymes containing spinophilin, neurabin, and selected catalytic subunit isoforms [10].
• Spinophilin, a novel protein phosphatase 1 binding protein localized to dendritic spines [11].
• F-actin co-sedimentation and overlay analysis revealed that phosphorylation of spinophilin reduced the stoichiometry of the spinophilin-actin interaction [12].
• Spinophilin is a protein phosphatase 1 (PP1)- and actin-binding protein that modulates excitatory synaptic transmission and dendritic spine morphology [12].
• Characterization of the neuronal targeting protein spinophilin and its interactions with protein phosphatase-1 [13].

Anatomical context of Ppp1r9b

• These results suggest that neurabin-II/spinophilin plays an important role in linking the actin cytoskeleton to the plasma membrane [14].
• The subcellular distribution analysis indicated that neurabin-II was enriched at the postsynaptic density fraction in rat brain and the adherens junction fraction in rat liver [14].
• Within the brain this protein displays a remarkably distinct localization to the heads of dendritic spines and has therefore been named spinophilin [11].
• Phosphorylation of spinophilin modulates its interaction with actin filaments [12].
• Immunocytochemistry in epithelial cells and cultured hippocampal neurons showed that endogenous neurabin II and I-2 colocalized at actin-rich structures, consistent with the ability of neurabins to target the PP1.I-2 complex to actin cytoskeleton and regulate cell morphology [15].

Associations of Ppp1r9b with chemical compounds

• Association of the D2 dopamine receptor third cytoplasmic loop with spinophilin, a protein phosphatase-1-interacting protein [16].
• [35S]Met-labeled 3i loops of the alpha2A AR (Val(217)-Ala(377)), alpha2BAR (Lys(210)-Trp(354)), and alpha2CAR (Arg(248)-Val(363)) subtypes interacted with glutathione S-transferase-spinophilin fusion proteins [17].
• We further show that, in hippocampus and ventral pallidum, spinophilin is occasionally present in dendritic shafts adjacent to gamma-aminobutyric acid-containing contacts [18].
• A 130-kDa glycoprotein (p130) has been found to be associated with surrogate light chain on pro- and pre-B I cells [19].
• Recombinant p150 formed a heterodimer with recombinant p130 as estimated by sucrose density gradient ultracentrifugation [20].

Physical interactions of Ppp1r9b

• Neurabin-II/spinophilin. An actin filament-binding protein with one pdz domain localized at cadherin-based cell-cell adhesion sites [14].

Other interactions of Ppp1r9b

• We purified from rat brain another F-actin-binding protein, which had a domain organization similar to that of neurabin but was ubiquitously expressed, and named it neurabin-II [14].
• Immunofluorescence microscopic analysis revealed that neurabin-II was highly concentrated at the synapse in primary cultured rat hippocampal neurons and at the cadherin-based cell-cell adhesion sites in Madin-Darby canine kidney cells [14].
• Because CREB has been linked to E induction of excitatory spine synapses, we used a spine marker, spinophilin, to establish E effects on spine formation [21].
• In this study, 2 days of estradiol-benzoate treatment produced significant and comparable increases in synaptophysin, syntaxin, and spinophilin immunoreactivity (IR) in the CA1 region of the dorsal hippocampus of ovariectomized female rats [22].
• Neurabin-II (spinophilin) is a ubiquitously expressed F-actin-binding protein containing an N-terminal actin-binding domain, a PDZ (PSD95/discs large/ZO-1) domain and a C-terminal domain predicted to form a coiled-coil structure [23].

Analytical, diagnostic and therapeutic context of Ppp1r9b

• Immunoprecipitation of spinophilin or neurabin from crude brain extracts selectively coprecipitated PP1gamma(1) over PP1beta [10].
• Using tryptic phosphopeptide mapping, site-directed mutagenesis, and microsequencing analysis, we identified two major sites of phosphorylation, Ser-94 and Ser-177, that are located within the actin-binding domain of spinophilin [12].
• The interaction is not mediated via the unique 29-amino acid insert in D2long; both D2long and D2short third cytoplasmic loops interact with spinophilin in vitro and in yeast two-hybrid assays [16].
• Here we report the molecular cloning of rat p130 by immunoaffinity purification [8].
• These results imply that RB2/p130 could be an important target for vascular gene therapy [1].

References