Pituitary adenylate cyclase-activating peptide stimulates neurite growth in PC12 cells

Hernandez, Ambrosio; Kimball, Beth C.; Romanchuk, Gail; Mulholland, Michael W.

doi:10.1016/0196-9781(95)00059-s

Cited by 51 publications

(49 citation statements)

References 30 publications

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“…TmACs are ubiquitously expressed, and their presence in PC12 cells was demonstrated biochemically and molecularly (30,31). In fact, they were shown to mediate the actions of PACAP (which is known to activate Rap1) in PC12 cells (14). To test whether NGF-induced activation of Rap1 is also mediated by tmACs, we assayed Rap1 activation by NGF and PACAP in the presence of a selective tmAC inhibitor.…”

Section: Ngf Signals Via Calcium To Raise Intracellular Camp and Actimentioning

confidence: 99%

“…In PC12 cells, tmACs can be activated by pituitary adenylyl cyclase-activating peptide (PACAP) via its specific G protein-coupled receptor PAC1 (12). Similar to NGF, PACAP activates Rap1 and elicits neurite outgrowth (13)(14)(15), but all attempts to link NGF or its receptors to tmAC activation have been unsuccessful. We have identified an additional, ubiquitously expressed (17,18) source of cAMP in mammalian cells, "soluble" adenylyl cyclase (sAC) (16).…”

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confidence: 99%

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Soluble Adenylyl Cyclase Mediates Nerve Growth Factor-induced Activation of Rap1

Stessin

Zippin

Kamenetsky³

et al. 2006

Journal of Biological Chemistry

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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.

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Section: Ngf Signals Via Calcium To Raise Intracellular Camp and Actimentioning

confidence: 99%

mentioning

confidence: 99%

Soluble Adenylyl Cyclase Mediates Nerve Growth Factor-induced Activation of Rap1

Stessin

Zippin

Kamenetsky³

et al. 2006

Journal of Biological Chemistry

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“…1). Although the PAC1 receptor couples to both G q and G s G proteins, PACAP-mediated neuritogenesis in PC12 cells is believed to proceed through cAMP because cAMP analogs or cAMP elevation with forskolin mimic the effects of PACAP (16,(20)(21)(22). In addition, neuritogenesis induced by PACAP is blocked by the cAMP antagonist dideoxyadenosine (22), and there is currently no evidence that direct activation of G q -mediated signaling mediates differentiation in PC12 cells.…”

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confidence: 99%

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

Gerdin

Eiden

2007

Sci. STKE

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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.

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“…PACAP, a key signal neuropeptide, has been proposed as an autocrine regulatory factor that plays a role in the differentiation of neural cortical precursor cells (47) and neurite outgrowth in PC12 cells (25,27,48). In addition, PACAP has been shown to play a negative role in neuronal proliferation (22,47,49,50).…”

Section: Effect Of Lot1 On Pac1-r Gene Expression and Activation Of Tmentioning

confidence: 99%

“…All three receptors activate adenylate cyclase through G s coupling, whereas PAC1-R also activates phospholipase C through G q coupling (24). It has been shown that in the PC12 cell line PACAP induces neurite generation (25,26) through the cAMP pathway (27,28). The finding that a correlation exists between the expression patterns of Lot1/ Zac1 and PAC1-R in some brain areas during development (11,13), that Lot1 expression is induced by the PACAP-cAMP system (16), and that Lot1 is capable of inducing transcription of the PAC1-R in different cell lines (29,30), suggests that Lot1 may be a key element of the pathway that mediates the various PACAP actions.…”

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confidence: 99%

Lot1 Is a Key Element of the Pituitary Adenylate Cyclase-activating Polypeptide (PACAP)/Cyclic AMP Pathway That Negatively Regulates Neuronal Precursor Proliferation

Fila

Trazzi

Crochemore

et al. 2009

Journal of Biological Chemistry

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Pituitary adenylate cyclase-activating peptide stimulates neurite growth in PC12 cells

Cited by 51 publications

References 30 publications

Soluble Adenylyl Cyclase Mediates Nerve Growth Factor-induced Activation of Rap1

Soluble Adenylyl Cyclase Mediates Nerve Growth Factor-induced Activation of Rap1

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

Lot1 Is a Key Element of the Pituitary Adenylate Cyclase-activating Polypeptide (PACAP)/Cyclic AMP Pathway That Negatively Regulates Neuronal Precursor Proliferation

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