Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RGS-GAIP (Galpha-interacting protein) is a member of the RGS (regulator of G protein signaling) family of proteins that functions to down-regulate Galphai/Galphaq-linked signaling. GAIP is a GAP or guanosine triphosphatase-activating protein that was initially discovered by virtue of its ability to bind to the heterotrimeric G protein Galphai3, which is found on both the plasma membrane (PM) and Golgi membranes. Previously, we demonstrated that, in contrast to most other GAPs, GAIP is membrane anchored and palmitoylated. In this work we used cell fractionation and immunocytochemistry to determine with what particular membranes GAIP is associated. In pituitary cells we found that GAIP fractionated with intracellular membranes, not the PM; by immunogold labeling GAIP was found on clathrin-coated buds or vesicles (CCVs) in the Golgi region. In rat liver GAIP was concentrated in vesicular carrier fractions; it was not found in either Golgi- or PM-enriched fractions. By immunogold labeling it was detected on clathrin-coated pits or CCVs located near the sinusoidal PM. These results suggest that GAIP may be associated with both TGN-derived and PM-derived CCVs. GAIP represents the first GAP found on CCVs or any other intracellular membranes. The presence of GAIP on CCVs suggests a model whereby a GAP is separated in space from its target G protein with the two coming into contact at the time of vesicle fusion.
Mol Biol Cell 1998 May
PMID:RGS-GAIP, a GTPase-activating protein for Galphai heterotrimeric G proteins, is located on clathrin-coated vesicles. 957 Dec 44

Nuclear receptors regulate transcription by binding to specific DNA response elements of target genes. Herein, we report the molecular cloning and characterization of a novel Xenopus cDNA encoding a transcription coactivator xSRC-3 by using retinoid X receptor (RXR) as a bait in the yeast two-hybrid screening. It belongs to a growing coactivator family that includes a steroid receptor coactivator amplified in breast cancer (AIB1), p300/ CREB-binding protein (CBP)-interacting protein (p/ CIP), and transcriptional intermediate factor 2 (TIF2). It also interacts with a series of nuclear receptors including retinoic acid receptor (RAR), thyroid hormone receptor (TR), and orphan nuclear receptors [hepatocyte nuclear receptor 4 (HNF4) and constitutive androstane receptor (CAR)]. However, it does not interact with small heterodimer partner (SHP), an orphan nuclear receptor known to antagonize ligand-dependent transactivation of other nuclear receptors. In CV-1 cells, cotransfection of xSRC-3 differentially stimulates ligand-induced transactivation of RXR, TR, and RAR in a dose-dependent manner. Interestingly, xSRC-3 is highly expressed in adult liver and early stages of oocyte development, suggesting that studies of xSRC-3 may lead to better understanding of the roles nuclear receptors play in oocyte development as well as liver-specific gene expression.
Mol Endocrinol 1998 Jul
PMID:Molecular cloning of xSRC-3, a novel transcription coactivator from Xenopus, that is related to AIB1, p/CIP, and TIF2. 965 7

Nuclear hormone receptors exert transcriptional activation of target genes upon hormone induction via interactions with the basal transcription machinery. This interaction is mediated by cofactors which physically bind to receptors, thereby acting as coactivators or corepressors leading to activation or repression, respectively. Here we report the screening for and cloning of a peroxisome proliferator receptor-interacting protein, the rat homolog of TIF2. By sequence comparison with the related coactivator SRC-1, we identified three short conserved motifs (NR boxes) in both proteins which are the putative binding sites of TIF2 to nuclear hormone receptors. We demonstrate here by generation of amino acid exchanges within the NR boxes that all three boxes located in the receptor interaction domain of TIF2 are necessary and sufficient for interaction. The three boxes individually can bind to hormone receptors but display preferences in binding for certain receptors. In addition, we show that the interaction domain of TIF2 can compete with other AF-2-dependent cofactors for binding to receptors. Finally, we demonstrate cooperative binding of two TIF2 molecules to a heterodimeric nuclear receptor complex even in the presence of only one cognate ligand, indicating an allosteric effect on the heterodimeric partner upon coactivator binding.
Mol Cell Biol 1998 Oct
PMID:Mechanistic principles in NR box-dependent interaction between nuclear hormone receptors and the coactivator TIF2. 974 17

The mouse homologue of the human receptor-interacting protein 140 (RIP140) was isolated from a mouse embryonic cDNA library in yeast two-hybrid screening experiments by using the ligand binding domain (LBD) of nuclear orphan receptor TR2 as the bait. The receptor-interacting domains of mouse RIP140 were mapped to the regions containing the LXXLL motif (where L is leucine and X is any amino acid), and the RIP140-interacting domain of TR2 was mapped to its C-terminal 10- to 20-amino-acid sequence, a putative activation function 2 (AF-2) region. In a GAL4 reporter system and a reporter driven by the proximal region of the TR2 promoter, RIP140 functioned as a corepressor for both a GAL4 DNA binding domain (BD)-TR2 fusion and the wild-type receptor. When tethered to the BD of GAL4, RIP140 exerted a trans-repressive effect on the GAL4 reporter. In addition, RIP140 suppressed the retinoic acid (RA) receptor-mediated RA induction in a dose-dependent manner. Finally, it was demonstrated that in the presence of RIP140, a cytosolic, green fluorescent protein-tagged TR2 LBD translocated into the nucleus, and TR2 and RIP140 were coimmunoprecipitated from the cell extract, indicating that the interaction between RIP140 and the LBD of TR2 occurred in vivo. The potential biological role of RIP140 in TR2-modulated transcriptional activity is discussed.
Mol Cell Biol 1998 Nov
PMID:Cloning and characterization of mouse RIP140, a corepressor for nuclear orphan receptor TR2. 977 88

Rac3 is a small GTPase of the Rho family, members of which have been implicated in tumorigenesis, cell growth/death and organization of the actin cytoskeleton. Many Rac-interacting proteins or effectors identified to date have a role in cytoskeletal organization. Using the yeast two-hybrid system, we have isolated a novel Rac3-interacting protein from a human placenta cDNA library which has no homology to other previously identified Rac-interacting proteins. Sequence analysis revealed that this protein is C1D, the human homolog of the murine SUN-CoR protein which acts as a corepressor for the thyroid hormone receptor. In yeast cells, C1D binds to constitutively activated but not to GDP-bound Rac3. When coexpressed with Rac3 in COS cells, C1D complexed with constitutively active Rac3 but not with wild-type Rac3, demonstrating that C1D-Rac3 interactions take place in vivo in mammalian cells and that C1D appears to be an effector of Rac3. The C1D gene was mapped to human chromosome 2, which frequently shows deletions in human follicular thyroid carcinomas.
Int J Mol Med 1998 Apr
PMID:Identification of a novel Rac3-interacting protein C1D. 985 80

Ras-related, guanine nucleotide-binding proteins of the Ypt/Rab family play a key role at defined steps in vesicular transport, both in yeast and in mammalian cells. In yeast, Ypt1p has an essential function late in endoplasmic reticulum (ER) to Golgi transport, and the redundant Ypt31/Ypt32 GTPases have been proposed to act in transport through and/or from the Golgi. Here we report that mutant alleles of YPT31 and YPT32, whose gene products have a reduced affinity for GTP, are able to suppress the dominant lethal phenotype of YPT1(N121I). Co-expression of YPT1(N121I) and the suppressor YPT31(N126I) allow essentially undisturbed secretory transport in the absence of the respective wild-type GTPases. Such mutant cells massively overaccumulate 60-100 nm vesicles and are heat sensitive. It appears likely that the mutant GTPases, which are defective in nucleotide binding, compete for the binding of common interacting protein(s). These and other genetic interactions between YPT1, YPT31/32, ARF1 and SEC4 described here strongly support the view that Ypt31p and Ypt32p have a central, Golgi-associated function in anterograde or retrograde transport.
Mol Gen Genet 1999 Feb
PMID:Functional implications of genetic interactions between genes encoding small GTPases involved in vesicular transport in yeast. 1007 Dec 13

In order to aid in an understanding of the cellular functions of protein kinase CK2, a search for interacting proteins was carried out using a 32P-labeled CK2 overlay method. Several proteins were found to associate with CK2 by this assay; among them, one protein of 110 kDa appeared to be the most prominent one. The possible association of CK2 with p110 was suggested by experiments involving the co-immunoprecipitation using anti-CK2 antibodies. Further analysis using GST-CK2 fusion proteins demonstrated that the CK2-p110 interaction occurred through the CK2alpha/alpha' subunits. To identify p110, it was purified using a GST-CK2 affinity column, and internal amino acid sequencing was then performed. p110 was found to be nucleolin, a nucleolar protein that may be important for rRNA synthesis; a possible role of CK2 in the control of this process is suggested. Using the same CK2 overlay technique, another interacting protein, insulin receptor substrate 1 (IRS-1), was also identified. By applying a modified overlay method using individual 35S-labeled CK2 subunits, obtained by in vitro translation in rabbit reticulate lysates, it was determined that CK2 associates with IRS-1 through its alpha/alpha' subunits; i.e. in keeping with the fact that IRS-1 is a known substrate for CK2. However, further work is needed to examine the association of CK2 with IRS-1 in vivo in order to fully understand the significance of the interaction.
Mol Cell Biochem 1999 Jan
PMID:Identification of proteins that associate with protein kinase CK2. 1009 12

Signalling via the protein kinase Raf-MEK-ERK pathway is of major importance for transformation by oncogenes. To identify genes affected by inhibition of this pathway, c-JUN transformed rat fibroblasts were treated with a MEK1 inhibitor (PD98059) and subjected to two-dimensional gel electrophoresis after cell lysis. Gene products with expression influenced by MEK1 inhibition were determined by mass spectrometry of fragments from in-gel tryptic digestions. The expression of pirin, a nuclear factor I-interacting protein, was lowered after inhibition of MEK1. Western blot analysis revealed increased expression of pirin in RAS and c-JUN transformed cells in the absence of PD98059. Inhibition of MEK1 also led to reduced expression of alpha-enolase, phosphoglycerate kinase, elongation factor 2 and heterogeneous nuclear ribonucleoprotein A3, the latter two being detected as truncated proteins. In contrast, the level of ornithine aminotransferase was increased. We conclude that inhibition of MEK1 results in major alterations of protein expression in c-JUN transformed cells, suggesting that this pathway is important for oncogene-induced phenotypic changes.
Cell Mol Life Sci 1999 Mar
PMID:Protein kinase-dependent overexpression of the nuclear protein pirin in c-JUN and RAS transformed fibroblasts. 1022 60

We have screened for proteins that interact with v-SNAREs of the late secretory pathway in the yeast Saccharomyces cerevisiae. A novel protein, designated Vsm1, binds tightly to the Snc2 v-SNARE in the two-hybrid system and can be coimmunoprecipitated with Snc1 or Snc2 from solubilized yeast cell extracts. Disruption of the VSM1 gene results in an increase of proteins secreted into the medium but does not affect the processing or secretion of invertase. In contrast, VSM1 overexpression in cells which bear a temperature-sensitive mutation in the Sec9 t-SNARE (sec9-4 cells) results in the accumulation of non-invertase-containing low-density secretory vesicles, inhibits cell growth and the secretion of proteins into the medium, and blocks rescue of the temperature-sensitive phenotype by SNC1 overexpression. Yet, VSM1 overexpression does not affect yeast bearing a sec9-7 allele which, in contrast to sec9-4, encodes a t-SNARE protein capable of forming a stable SNARE complex in vitro at restrictive temperatures. On the basis of these results, we propose that Vsm1 is a novel v-SNARE-interacting protein that appears to act as negative regulator of constitutive exocytosis. Moreover, this regulation appears specific to one of two parallel exocytic paths which are operant in yeast cells.
Mol Cell Biol 1999 Jun
PMID:Yeast VSM1 encodes a v-SNARE binding protein that may act as a negative regulator of constitutive exocytosis. 1033 Jan 87

Transcriptional responses to estrogens are controlled by the cell- and gene-specific interactions of the nuclear estrogen receptor (ER) with cofactors and other transcription factors. The pituitary-specific PRL enhancer/promoter is regulated by estrogens only when it is bound by both ER and the pituitary-specific transcription factor, Pit-1. Cooperative ER/Pit-1 activation of the dormant PRL enhancer/promoter in pituitary progenitor cells requires the estrogen-dependent activation function-2 (AF-2) of ER, but is inhibited by one AF-2-interacting cofactor, RIP140. Here, the complex actions of RIP140 and other AF-2-interacting proteins at the PRL enhancer/promoter were shown to operate via ER itself. RIP140 inhibition of ER/Pit-1 activation in the absence of AF-1 and RIP140 inhibition of both ER alpha and ER beta cooperative activation with Pit-1 suggested a conserved ER site for RIP140 action, possibly AF-2. Coexpression of other AF-2-interacting proteins, including the p160 factors, steroid receptor coactivator-1a (SRC-1a) and glucocorticoid receptor interacting protein-1 (GRIP1), had negligible effects on ER alpha/Pit-1 cooperative activation, but partially relieved RIP140 inhibition. Relief of RIP140 inhibition required the AF-2-binding, LXXLL motifs in SRC-1a and GRIP1. An ER AF-2 mutant that selectively blocked ER interaction with p160s, but not RIP140, still cooperated with Pit-1 and was inhibited by RIP140, but was not relieved by SRC-1a or GRIP1 expression. Thus, SRC-1a and GRIP1 binding to AF-2 counteracted the inhibition of ER/Pit-1 activation by another AF-2-interacting protein, RIP140. Complex, sometimes antagonistic, actions of different classes of AF-2-interacting proteins may play an important role in the cell- and gene-specific estrogen regulation of PRL and other genes.
Mol Endocrinol 1999 Jun
PMID:Regulation of estrogen receptor activation of the prolactin enhancer/promoter by antagonistic activation function-2-interacting proteins. 1037 92


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