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Sci. STKE, 17 April 2007
Vol. 2007, Issue 382, p. pe15
[DOI: 10.1126/stke.3822007pe15]


Regulation of PC12 Cell Differentiation by cAMP Signaling to ERK Independent of PKA: Do All the Connections Add Up?

Matthew J. Gerdin* and Lee E. Eiden

Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institutes of Health, 9000 Rockville Pike, Building 49, Room 5A27, Bethesda, MD 20892, USA.

Abstract: Pituitary adenylate cyclase–activating polypeptide (PACAP) is a neuropeptide that elevates adenosine 3',5'-monophosphate (cyclic AMP, also abbreviated cAMP) to elicit neuritogenesis in PC12 cells. This effect appears to be independent of cAMP-dependent protein kinase (PKA) yet dependent on cAMP, leading to the conclusion that another cAMP-binding protein and subsequent signaling pathway must exist to mediate this PKA-independent signaling mechanism. Such a protein was identified as exchange protein directly activated by cAMP (EPAC). Although EPAC may play an indirect role in PACAP-mediated neuritogenesis, it does not serve as the only PKA-independent link from cAMP that leads to neuritogenesis. Thus, the challenge remains to construct a signaling network that incorporates the known mediators, working independently of PKA, that are ultimately responsible for PACAP-mediated neuritogenesis.

*Corresponding author. Telephone, 301-435-4105; e-mail, matthewgerdin{at}

Citation: M. J. Gerdin, L. E. Eiden, Regulation of PC12 Cell Differentiation by cAMP Signaling to ERK Independent of PKA: Do All the Connections Add Up? Sci. STKE 2007, pe15 (2007).

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