Sustained GRK2-dependent CREB activation is essential for α2-adrenergic receptor-induced PC12 neuronal differentiation.

Sustained GRK2-dependent CREB activation is essential for α2-adrenergic receptor-induced PC12 neuronal differentiation. Cell Signal. 2019 Oct 31;:109446 Authors: Karkoulias G, McCrink KA, Maning J, Pollard CM, Desimine VL, Patsouras N, Psallidopoulos M, Taraviras S, Lymperopoulos A, Flordellis C Abstract Many aspects of neuronal development, such as neuronal survival and differentiation, are regulated by the transcription factor cAMP-response element-binding protein (CREB). We have previously reported that α2-adrenergic receptors (ARs), members of the G protein-coupled receptor (GPCR) superfamily, induce neuronal differentiation of rat pheochromocytoma (PC)-12 cells in a subtype-specific manner, i.e. α2A<α2B<α2C. Herein, we sought to investigate CREB`s involvement in this α2AR-dependent neurogenic process. We used a combination of gene reporter assays and immunoblotting analysis, coupled with co-immunoprecipitation and morphological analysis, in transfected PC12 cell lines. Chronic α2B- or α2C-AR activation results in sustained CREB activation, which is both necessary and sufficient for neuronal differentiation of PC12 cells expressing these two α2ARs. In contrast, chronic α2A activation only leads to transient CREB activation, insufficient for PC12 neuronal differentiation. However, upon CREB overexpression, α2A-AR triggers neuronal differentiation similarly to α2B- or α2C-ARs. Importantly, NGF (Nerve Growth Facto...
Source: Cellular Signalling - Category: Cytology Authors: Tags: Cell Signal Source Type: research