Tags

Type your tag names separated by a space and hit enter

Depolarization-induced differentiation of PC12 cells is mediated by phospholipase D2 through the transcription factor CREB pathway.
J Neurochem. 2008 Mar; 104(5):1372-86.JN

Abstract

The present study examined the role of phospholipase D2 (PLD2) in the regulation of depolarization-induced neurite outgrowth and the expression of growth-associated protein-43 (GAP-43) and synapsin I in rat pheochromocytoma (PC12) cells. Depolarization of PC12 cells with 50 mmol/L KCl increased neurite outgrowth and elevated mRNA and protein expression of GAP-43 and synapsin I. These increases were suppressed by inhibition of Ca2+-calmodulin-dependent protein kinase II (CaMKII), PLD, or mitogen-activated protein kinase kinase (MEK). Knockdown of PLD2 by small interfering RNA (siRNA) suppressed the depolarization-induced neurite outgrowth, and the increase in GAP-43 and synapsin I expression. Depolarization evoked a Ca2+ rise that activated various signaling enzymes and the cAMP response element-binding protein (CREB). Silencing CaMKIIdelta by siRNA blocked KCl-induced phosphorylation of proline-rich protein tyrosine kinase 2 (Pyk2), Src kinase, and extracellular signal-regulated kinase (ERK). Inhibition of Src or MEK abolished phosphorylation of ERK and CREB. Furthermore, phosphorylation of Pyk2, ERK, and CREB was suppressed by the PLD inhibitor, 1-butanol and transfection of PLD2 siRNA, whereas it was enhanced by over-expression of wild-type PLD2. Depolarization-induced PLD2 activation was suppressed by CaMKII and Src inhibitors, but not by MEK or protein kinase A inhibitors. These results suggest that the signaling pathway of depolarization-induced PLD2 activation was downstream of CaMKIIdelta and Src, and upstream of Pyk2(Y881) and ERK/CREB, but independent of the protein kinase A. This is the first demonstration that PLD2 activation is involved in GAP-43 and synapsin I expression during depolarization-induced neuronal differentiation in PC12 cells.

Authors+Show Affiliations

Department of Cell Signaling, Gifu University Graduate School of Medicine, Gifu, Japan. yobanno@gifu-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18004999

Citation

Banno, Yoshiko, et al. "Depolarization-induced Differentiation of PC12 Cells Is Mediated By Phospholipase D2 Through the Transcription Factor CREB Pathway." Journal of Neurochemistry, vol. 104, no. 5, 2008, pp. 1372-86.
Banno Y, Nemoto S, Murakami M, et al. Depolarization-induced differentiation of PC12 cells is mediated by phospholipase D2 through the transcription factor CREB pathway. J Neurochem. 2008;104(5):1372-86.
Banno, Y., Nemoto, S., Murakami, M., Kimura, M., Ueno, Y., Ohguchi, K., Hara, A., Okano, Y., Kitade, Y., Onozuka, M., Murate, T., & Nozawa, Y. (2008). Depolarization-induced differentiation of PC12 cells is mediated by phospholipase D2 through the transcription factor CREB pathway. Journal of Neurochemistry, 104(5), 1372-86.
Banno Y, et al. Depolarization-induced Differentiation of PC12 Cells Is Mediated By Phospholipase D2 Through the Transcription Factor CREB Pathway. J Neurochem. 2008;104(5):1372-86. PubMed PMID: 18004999.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Depolarization-induced differentiation of PC12 cells is mediated by phospholipase D2 through the transcription factor CREB pathway. AU - Banno,Yoshiko, AU - Nemoto,Satoshi, AU - Murakami,Masashi, AU - Kimura,Masashi, AU - Ueno,Yoshihito, AU - Ohguchi,Kenji, AU - Hara,Akira, AU - Okano,Yukio, AU - Kitade,Yukio, AU - Onozuka,Minoru, AU - Murate,Takashi, AU - Nozawa,Yoshinori, Y1 - 2007/11/14/ PY - 2007/11/17/pubmed PY - 2008/3/15/medline PY - 2007/11/17/entrez SP - 1372 EP - 86 JF - Journal of neurochemistry JO - J Neurochem VL - 104 IS - 5 N2 - The present study examined the role of phospholipase D2 (PLD2) in the regulation of depolarization-induced neurite outgrowth and the expression of growth-associated protein-43 (GAP-43) and synapsin I in rat pheochromocytoma (PC12) cells. Depolarization of PC12 cells with 50 mmol/L KCl increased neurite outgrowth and elevated mRNA and protein expression of GAP-43 and synapsin I. These increases were suppressed by inhibition of Ca2+-calmodulin-dependent protein kinase II (CaMKII), PLD, or mitogen-activated protein kinase kinase (MEK). Knockdown of PLD2 by small interfering RNA (siRNA) suppressed the depolarization-induced neurite outgrowth, and the increase in GAP-43 and synapsin I expression. Depolarization evoked a Ca2+ rise that activated various signaling enzymes and the cAMP response element-binding protein (CREB). Silencing CaMKIIdelta by siRNA blocked KCl-induced phosphorylation of proline-rich protein tyrosine kinase 2 (Pyk2), Src kinase, and extracellular signal-regulated kinase (ERK). Inhibition of Src or MEK abolished phosphorylation of ERK and CREB. Furthermore, phosphorylation of Pyk2, ERK, and CREB was suppressed by the PLD inhibitor, 1-butanol and transfection of PLD2 siRNA, whereas it was enhanced by over-expression of wild-type PLD2. Depolarization-induced PLD2 activation was suppressed by CaMKII and Src inhibitors, but not by MEK or protein kinase A inhibitors. These results suggest that the signaling pathway of depolarization-induced PLD2 activation was downstream of CaMKIIdelta and Src, and upstream of Pyk2(Y881) and ERK/CREB, but independent of the protein kinase A. This is the first demonstration that PLD2 activation is involved in GAP-43 and synapsin I expression during depolarization-induced neuronal differentiation in PC12 cells. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/18004999/Depolarization_induced_differentiation_of_PC12_cells_is_mediated_by_phospholipase_D2_through_the_transcription_factor_CREB_pathway_ L2 - https://doi.org/10.1111/j.1471-4159.2007.05085.x DB - PRIME DP - Unbound Medicine ER -