Regulation of PC12 cell differentiation by cAMP signaling to ERK independent of PKA: do all the connections add up?
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.
Gerdin
Matthew J
MJ
Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institutes of Health, Bethesda, MD 20892, USA. matthewgerdin@mail.nih.gov
Eiden
Lee E
LE
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D015290:Second Messenger Systems / Q000502:physiology*
D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases