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CREB phosphorylation and melatonin biosynthesis in the rat pineal gland: Involvement of cyclic AMP dependent protein kinase type II
Author(s) -
Maronde Erik,
Wicht Helmut,
Taskén Kjetil,
Genieser HansGottfried,
Dehghani Faramarz,
Olcese James,
Korf HorstWerner
Publication year - 1999
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.1999.tb00613.x
Subject(s) - creb , protein kinase a , pinealocyte , melatonin , pineal gland , map2k7 , phosphorylation , biology , mitogen activated protein kinase kinase , cyclin dependent kinase 2 , cgmp dependent protein kinase , protein phosphorylation , c raf , ask1 , cyclic amp response element binding protein , biochemistry , endocrinology , transcription factor , gene
Phosphorylation of cyclic AMP response element binding protein (CREB) at amino acid serine 133 appears as an important link between the norepinephrine (NE)‐induced activation of second messenger systems and the stimulation of melatonin biosynthesis. Here we investigated in the rat pineal gland: 1) the type of protein kinase that mediates CREB phosphorylation; and 2) its impact on melatonin biosynthesis. Immunochemical or immunocytochemical demonstration of serine 133 ‐phosphorylated cyclic AMP regulated element binding protein (pCREB) and radioimmunological detection of melatonin revealed that only cyclic AMP‐dependent protein kinase (PKA) inhibitors suppressed NE‐induced CREB phosphorylation and stimulation of melatonin biosynthesis, whereas inhibitors of cyclic GMP‐dependent protein kinase (PKG), mitogen‐activated protein kinase kinase, protein kinase C, or calcium‐calmodulin‐dependent protein kinase (CaMK) were ineffective. Investigations with cyclic AMP‐agonist pairs that selectively activate either PKA type I or II link NE‐induced CREB phosphorylation and stimulation of melatonin biosynthesis to the activation of PKA type II. Our data suggest that PKA type II plays an important role in the transcriptional control of melatonin biosynthesis in the rat pineal organ.