RGD Reference Report - Soluble adenylyl cyclase mediates nerve growth factor-induced activation of Rap1. - Rat Genome Database

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Soluble adenylyl cyclase mediates nerve growth factor-induced activation of Rap1.

Authors: Stessin, AM  Zippin, JH  Kamenetsky, M  Hess, KC  Buck, J  Levin, LR 
Citation: Stessin AM, etal., J Biol Chem. 2006 Jun 23;281(25):17253-8. Epub 2006 Apr 20.
RGD ID: 2313173
Pubmed: (View Article at PubMed) PMID:16627466
DOI: Full-text: DOI:10.1074/jbc.M603500200

Nerve growth factor (NGF) and the ubiquitous second messenger cyclic AMP (cAMP) are both implicated in neuronal differentiation. Multiple studies indicate that NGF signals to at least a subset of its targets via cAMP, but the link between NGF and cAMP has remained elusive. Here, we have described the use of small molecule inhibitors to differentiate between the two known sources of cAMP in mammalian cells, bicarbonate- and calcium-responsive soluble adenylyl cyclase (sAC) and G protein-regulated transmembrane adenylyl cyclases. These inhibitors, along with sAC-specific small interfering RNA, reveal that sAC is uniquely responsible for the NGF-elicited rise in cAMP and is essential for the NGF-induced activation of the small G protein Rap1 in PC12 cells. In contrast and as expected, transmembrane adenylyl cyclase-generated cAMP is responsible for Rap1 activation by the G protein-coupled receptor ligand PACAP (pituitary adenylyl cyclase-activating peptide). These results identify sAC as a mediator of NGF signaling and reveal the existence of distinct pathways leading to cAMP-dependent signal transduction.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component
cytoplasm  (IDA)

Objects Annotated

Genes (Rattus norvegicus)
Adcy10  (adenylate cyclase 10)


Additional Information