Activation of the CRF1 receptor causes ERK1/2 mediated increase in GRK3 expression in CATH.a cells

G-protein coupled receptor kinase 3 (GRK3) mediates desensitization of alpha2-adrenergic (α2-AR) and CRF1 receptors. CRF1 receptors, α2-AR and GRK3, are localized to the primary source of noradrenergic inputs to higher brain centers critical in both the response to stress and the development of depression, namely, locus coeruleus (LC). This study utilizing CATH.a cells (derived from the LC), demonstrates for the first time, that the stress hormone, CRF selectively up-regulates GRK3 expression via an ERK1/2-mediated mechanism accompanied by the activation of Sp-1 and Ap-2 transcription factors. This observation has important implications for the regulation of stress signaling in the brain.