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Differentiation‐induced alterations in cyclic AMP signaling in the Cath.a differentiated (CAD) neuronal cell line
Author(s) -
Johnston Christopher A.,
Beazely Michael A.,
Bilodeau Matthew L.,
Andrisani Ourania,
Watts Val J.
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2004.02285.x
Subject(s) - forskolin , cellular differentiation , microbiology and biotechnology , signal transduction , protein kinase a , adenylate kinase , biology , intracellular , receptor , cyclic amp response element binding protein , cyclic adenosine monophosphate , cyclase , phosphorylation , endocrinology , transcription factor , creb , biochemistry , gene
Regulation of intracellular cyclic AMP is critical to the modulation of many cellular activities, including cellular differentiation. Moreover, morphological differentiation has been linked to subsequent alterations in the cAMP signaling pathway in various cellular models. The current study was designed to explore the mechanism for the previously reported enhancement of adenylate cyclase activity in Cath.a differentiated cells following differentiation. Differentiation of Cath.a differentiated cells stably expressing the D 2L dopamine receptor markedly potentiated both forskolin‐ and A 2 ‐adenosine receptor‐stimulated cAMP accumulation. This enhancement was accompanied by a twofold increase in adenylate cyclase 6 (AC6) expression and a dramatic loss in the expression of AC9. The ability of Ca 2+ to inhibit drug‐stimulated cAMP accumulation was enhanced following differentiation, as was D 2L dopamine receptor‐mediated inhibition of Gα s ‐stimulated cAMP accumulation. Differentiation altered basal and drug‐stimulated phosphorylation of the cAMP‐response element‐binding protein, which was independent of changes in protein kinase A expression. The current data suggest that differentiation of the neuronal cell model, Cath.a differentiated cells induces significant alterations in the expression and function of both the proximal and distal portions of the cAMP signaling pathway and may impact cellular operations dependent upon this pathway.