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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

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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.

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