Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Microarray gene expression profiling of kinase-dependent and kinase-independent effects of GRK2

ABSTRACT: The ubiquitously expressed G-protein-coupled receptor kinase 2 (GRK2, ADRBK1) is an indispensable kinase involved in growth, differentiation and development. Exaggerated GRK2 activity plays a major pathophysiological role in the development of cardiovascular diseases such as heart failure and hypertension. GRK2 exerts its functions by kinase-dependent and kinase-independent effects. To assess the differential impact of GRK2 on cellular signalling we established HEK cell clones with over-expression of comparable protein levels of GRK2 or the kinase-deficient GRK2-K220R mutant, respectively. HEK cells were either cultured in vitro or expanded in vivo, in immunodeficient NOD.Scid mice to discriminate between in vitro and in vivo effects of GRK2. Whole genome microarray gene expression profiling was performed of cultured HEK cells and of NOD.Scid mouse-expanded HEK clones. As an additional control, cells were re-cultured in vitro after expansion in NOD.Scid mice.

ORGANISM(S): Homo sapiens

PROVIDER: GSE42771 | GEO | 2012/12/06

SECONDARY ACCESSION(S): PRJNA183101

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Microarray gene expression profiling of kinase-dependent and kinase-independent effects of GRK2

Project description:The ubiquitously expressed G-protein-coupled receptor kinase 2 (GRK2, ADRBK1) is an indispensable kinase involved in growth, differentiation and development. Exaggerated GRK2 activity plays a major pathophysiological role in the development of cardiovascular diseases such as heart failure and hypertension. GRK2 exerts its functions by kinase-dependent and kinase-independent effects. To assess the differential impact of GRK2 on cellular signalling we established HEK cell clones with over-expression of comparable protein levels of GRK2 or the kinase-deficient GRK2-K220R mutant, respectively. HEK cells were either cultured in vitro or expanded in vivo, in immunodeficient NOD.Scid mice to discriminate between in vitro and in vivo effects of GRK2. Whole genome microarray gene expression profiling was performed of cultured HEK cells and of NOD.Scid mouse-expanded HEK clones. As an additional control, cells were re-cultured in vitro after expansion in NOD.Scid mice. Whole genome microarray gene expression profiling was performed with three different study groups: (i) NOD.Scid mouse-expanded HEK clones expressing GRK2 or GRK2-K220R, (ii) cultured HEK cell clones expressing GRK2 or GRK2-K220R, and (iii) cell clones expressing GRK2 or GRK2-K220R, which were re-cultured after NOD.Scid mouse expansion.

2012-12-06 | E-GEOD-42771 | biostudies-arrayexpress

Whole genome cardiac gene expression profiling of transgenic mice with myocardium-specific expression of RKIP (PEBP1), kinase-inactive GRK2-K220R (ADRBK1-K220R), SCD1, and UCP1

Project description:The raf kinase inhibitor protein, RKIP, is up-regulated on cadiac biopsy specimens of heart failure patients. To investigate the in vivo role of an increased cardiac content of RKIP, we generated transgenic mice with myocardium-specific expression of RKIP (PEBP1; phosphatidylethanolamine binding protein 1) under control of the alpha-MHC promoter in B6 (C57BL/6J) background. Because RKIP is a dual-specific GRK2 and Raf kinase inhibitor, RKIP-transgenic mice were compared to transgenic mice with myocardium-specific expression of the GRK2 inhibitor, GRK2-K220R, which is a kinase-inactive GRK2 (ADRBK1) mutant with dominant-negative function. In frame of our studies, we found that RKIP-transgenic mice developed signs of heart failure and cardiotoxic lipid load at an age of 8 months. In contrast, transgenic expression of GRK2-K220R improved cardiac function and protected against chronic pressure overload-induced symptoms of heart failure. To identify genes related to cardiotoxic lipid load, we further determined the cardiac gene expression profile of Tg-SCD1 mice with mypcardium-specific expression of SCD1 (stearoyl-CoA desaturase-1) and Tg-UCP1 mice with heart-specific expression of UCP1 (uncoupling protein 1).

2018-09-18 | GSE120020 | GEO

Establishment of a novel model to assess the function of proteins under in vivo conditions

Project description:We established a novel model to assess the function of proteins under in vivo conditions. The model relies on the expansion of HEK293 cells in immunodeficient NOD.Scid mice. To validate the novel model, we performed microarray gene expression profiling of NOD.Scid-expanded HEK293 cells relative to conventionally cultivated cells. Microarray analysis revealed that cell expansion in NOD.Scid mice restored an imbalanced chaperone system without inducing a major upregulation of the entire protein folding machinery. Human embryonic kidney (HEK293) cells were injected subcutaneously into immunodeficient NOD.Scid mice. After three weeks, the expanded cell pellet was isolated, and total RNA was extracted. In parallel, total RNA was prepared from HEK293 cells cultivated in vitro under standard cell culture conditions in a commercially available medium containing 450 mg/dl glucose (DMEM). Microarray gene expression profiling was performed to determine differential gene expression between in vivo expanded and in vitro cultivated HEK293 cells. Two biological replicates for each condition were made (in vitro cultivated HEK293 cells: Cells-1 and Cells-2; and NOD.Scid-expanded HEK293 cells: Scid-1 and Scid-2).

2009-10-26 | E-GEOD-18739 | biostudies-arrayexpress

Cardiac transcriptome analysis of RKIP-transgenic and GRK2-transgenic mice by NGS

Project description:The RAF kinase inhibitor protein, RKIP, is a dual inhibitor of the RAF1 kinase and the G-protein-coupled receptor kinase 2 (GRK2). By inhibition of the proto-oncogenic and pro-survival RAF1-MAPK pathway, the RAF kinase inhibitor protein, RKIP, acts as a tumor suppressor, which enhances cardiomyocyte death and promotes the development of symptoms of heart failure. To elucidate pathomechanisms of heart failure induced by RKIP, the study determined the cardiac transcriptomes of eight-month-old, male, transgenic mice with cardiac-specific expression of RKIP (PEBP1) under control of the myocardium-specific, alpha-MHC promoter. In addition, the study determined the cardiac transcriptomes of GRK2-transgenic mice. Tg-GRK2 mice have a slightly increased transgenic expression of GRK2. According to NGS data, cardiac GRK2-Grk2 transcript levels of Tg-GRK2 mice are 1.59±0.10-fold higher than those of non-transgenic FVB hearts. In Tg-GRK2 mice, transgenic GRK2 is expressed under control of the ubiquitous CMV immediate-early promoter/enhancer. The non-transgenic control group are age-matched, male, nontransgenic FVB/N mice. NGS data of this study document transcriptome changes underlying the heart failure phenotype induced by transgenic RKIP expression and cardiac degeneration induced by GRK2 expression.

2021-12-27 | GSE191316 | GEO

G-protein coupled receptor kinase 2 safeguards epithelial phenotype in Head and Neck Squamous Cell Carcinomas.

Project description:Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal lining of the upper aerodigestive tract and display few treatment options in advanced stages. Despite increased knowledge of HNSCC molecular biology, the identification of new players involved in triggering HNSCC recurrence and metastatic disease is needed. We uncover that G-protein-coupled receptor kinase-2 (GRK2) expression is reduced in undifferentiated, high-grade human HNSCC tumors, whereas its silencing in model human HNSCC cells is sufficient to trigger epithelial-to-mesenchymal transition (EMT) phenotypic features, an EMT-like transcriptional program and enhanced lymph node colonization from orthotopic tongue tumors in mice. Conversely, enhancing GRK2 expression counteracts mesenchymal cells traits by mechanisms involving phosphorylation and decreased functionality of the key EMT inducer Snail1. Our results suggest that GRK2 safeguards the epithelial phenotype, whereas its downregulation contributes to the activation of EMT programs in HNSCC

2019-12-31 | GSE111932 | GEO

Microarray gene expression profiling of transgenic mice with myocardium-specific expression of RKIP or a GRK-specific peptide inhibitor

Project description:The Raf kinase inhibitor protein (RKIP) is a dual inhibitor of the Raf kinase and the G-protein-coupled receptor kinase 2 (GRK2). GRK2 is an indispensable kinase, which exerts a major role in the pathogenesis of heart failure, and inhibition of GRK2 is cardioprotective in experimental models of heart failure. To investigate the cardiac function of RKIP as GRK2 inhibitor, we generated transgenic mice with myocardium-specific expression of RKIP under control of the alpha-MHC promoter. For comparison, mice with myocardium-specific expression of a GRK-specific peptide inhibitor (GRK-Inh) were also generated. Two different transgenic mouse models were established. Transgenic RKIP mice and transgenic GRK-Inh mice were born at Mendelian frequencey and grew to adulthood normally.

2012-12-06 | GSE42753 | GEO

Expression data from adult (9 month-old) hearts from GRK2 heterozygous C57BL/6J mice and its wild type littermates

Project description:G protein-coupled receptor kinase 2 (GRK2) has emerged as a key regulator of cardiac function and myocardial structure. Cardiac GRK2 is increased in heart failure and ischemia in humans, whereas genetic inhibition of GRK2 is cardioprotective in animal models of these pathologies. However, the mechanistic basis underlying these effects are not fully understood. We have used adult GRK2 hemizygous mice (GRK2+/-) as a model to assess the effects of a sustained systemic inhibition of GRK2 in heart tissue with age. We used microarrays to determine the global programme of gene expression underlying cardioprotection in GRK2 hemizygous mice.

2012-10-20 | GSE41706 | GEO

Expression data from adult (9 month-old) and young (4 month-old) hearts from GRK2 heterozygous C57BL/6J mice.

2012-10-25 | GSE41808 | GEO

Expression data from young (4 month-old) hearts from GRK2 heterozygous C57BL/6J mice and its wild type littermates

2012-10-25 | GSE41809 | GEO

Expression data from adult (9 month-old) and young (4 month-old) hearts from C57BL/6J mice

2012-10-25 | GSE41807 | GEO