Activation of the CRF(1) receptor causes ERK1/2 mediated increase in GRK3 expression in CATH.a cells.
G-protein coupled receptor kinase 3 (GRK3) mediates desensitization of alpha(2)-adrenergic (alpha(2)-AR) and CRF(1) receptors. CRF(1) receptors, alpha(2)-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.
Salim
Samina
S
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204-5037, USA.
Hite
Brian
B
Eikenburg
Douglas C
DC
D000818:Animals; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D054770:G-Protein-Coupled Receptor Kinase 3; D005786:Gene Expression Regulation / Q000187:drug effects; D008125:Locus Coeruleus / Q000166:cytology / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000378:metabolism; D051552:beta-Adrenergic Receptor Kinases / Q000235:genetics* / Q000378:metabolism; D000099052:CRF Receptor, Type 1
D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D016329:Sp1 Transcription Factor; D050656:Transcription Factor AP-2; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D054770:G-Protein-Coupled Receptor Kinase 3; C517851:Grk3 protein, rat; D051552:beta-Adrenergic Receptor Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3