title: ERK-regulated double cortin-like kinase (DCLK)-short phosphorylation and nuclear translocation stimulate POMC gene expression in endocrine melanotrope cells.
abstract: We tested whether double cortin-like kinase-short (DCLK-short), a microtubule-associated Ser/Thr kinase predominantly expressed in the brain, is downstream of the ERK signaling pathway and is involved in proopiomelanocortin gene (POMC) expression in endocrine pituitary melanotrope cells of Xenopus laevis. Melanotropes form a well-established model to study physiological aspects of neuroendocrine plasticity. The amphibian X. laevis adapts its skin color to the background light intensity by the release of α-MSH from the melanotrope cell. In frogs on a white background, melanotropes are inactive but they are activated during adaptation to a black background. Our results show that melanotrope activation is associated with an increase in DCLK-short mRNA and with phosphorylation of DCLK-short at serine at position 30 (Ser-30). Upon cell activation phosphorylated Ser-30-DCLK-short was translocated from the cytoplasm into the nucleus, and the ERK blocker U0126 inhibited this process. The mutation of Ser-30 to alanine also inhibited the translocation and reduced POMC expression, whereas overexpression stimulated POMC expression. This is the first demonstration of DCLK-short in a native endocrine cell. We conclude that DCLK-short is physiologically regulated at both the level of its gene expression and protein phosphorylation and that the kinase is effectively regulating POMC gene expression upon its ERK-mediated phosphorylation.
authors: Department of Cellular Animal Physiology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Nijmegen, NL-6525 AJ Nijmegen, The Netherlands.
authors: Miyuki
authors: M
authors: Kuribara
authors: Bruce G
authors: BG
authors: Jenks
authors: Thomas F
authors: TF
authors: Dijkmans
authors: Daan
authors: D
authors: de Gouw
authors: Debbie T W M
authors: DT
authors: Ouwens
authors: Eric W
authors: EW
authors: Roubos
authors: Erno
authors: E
authors: Vreugdenhil
authors: Wim J J M
authors: WJ
authors: Scheenen
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D052717:Melanotrophs / Q000378:metabolism*; D010766:Phosphorylation; D011333:Pro-Opiomelanocortin / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D015854:Up-Regulation; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000235:genetics / Q000378:metabolism*
chemical_list: D029867:Xenopus Proteins; D011333:Pro-Opiomelanocortin; C568069:DCLK protein, Xenopus; D017346:Protein Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases