Predominant role by CaM kinase in NPY Y(1) receptor signaling: involvement of CREB [corrected].
The role of Ca(2+)/cAMP-dependent signal transduction and transcription factor CREB in mediating NPY- Y(1) receptor function was investigated in SK-N-MC cells. The Y(1) receptor agonist, [Leu(31),Pro(34)]-NPY, inhibited forskolin-stimulated cAMP production which was insensitive to thapsigargin or the CaM kinase II inhibitor, KN-93. Although activation of the Y(1) receptor leads to an increase in CREB phosphorylation, [Leu(31),Pro(34)]-NPY inhibited CREB phosphorylation in KN-93-treated cells. SK-N-MC cells were also transfected with PathDetect cis-CRE and trans-CREB/trans-cFos reporter genes to monitor the role of Ca(2+)/cAMP signals, triggered by Y(1) receptor, on reporter gene activity. Treatment of the cis-CRE-luciferase expression vector-transfected cells with [Leu(31),Pro(34)]-NPY increased reporter gene activity by 2 fold through a KN-93 sensitive pathway. In contrast, the peptide inhibited forskolin-stimulated luciferase activity. Consistently, [Leu(31),Pro(34)]-NPY induced trans-CREB mediated luciferase activity through a CaM kinase dependent pathway, and inhibited forskolin-stimulated luciferase gene expression. However, no effect of the peptide was observed on trans-cFos- mediated luciferase activity. These findings suggest that the NPY Y(1) receptor induces the expression of CRE containing target genes through the CaM kinase-CREB pathway, and inhibits CRE containing genes when cellular cAMP levels are elevated.[1]References
- Predominant role by CaM kinase in NPY Y(1) receptor signaling: involvement of CREB [corrected]. Sheriff, S., F Qureshy, A., T Chance, W., Kasckow, J.W., Balasubramaniam, A. Peptides (2002) [Pubmed]
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