Phospholipase D1 activation through Src and Ras is involved in basic fibroblast growth factor-induced neurite outgrowth of H19-7 cells.
Phospholipase D (PLD) is implicated in a variety of physiological processes that reveal it to be a member of the signal transducing phospholipases. We found that PLD1 is activated when basic fibroblast growth factor (bFGF) stimulates neurite outgrowth of an immortalized hippocampal cell line (H19-7). Overexpression of PLD1 in H19-7 cells dramatically elongated bFGF-induced neurite outgrowth and increased PLD activity. Transfection of DN-rPLD1 blocked bFGF-induced PLD activation and completely inhibited neurite outgrowth induced by bFGF, suggesting that PLD1 activation is important in bFGF-induced neurite outgrowth of H19-7 cells. PLD activation and neurite outgrowth induced by bFGF was dependent on phospholipase C gamma (PLC-gamma) and Ca2+, but not protein kinase C (PKC). Furthermore, inhibition of Src and Ras partially blocked bFGF-induced PLD activation and neurite outgrowth, respectively. Coinhibition of Src and Ras completely blocked bFGF-induced PLD activation, suggesting that Src and Ras independently regulate PLD1 activation. Interestingly, bFGF-induced PLD activation and neurite outgrowth did not require ERK1/2 activated by Ras. Taken together, this study demonstrates that bFGF activates PLD1 through PLC-gamma activation, which leads to neurite outgrowth in H19-7 cells. Furthermore, our results show that PLD1 activation by bFGF is regulated by Src and Ras independently.
Oh
Doo-Yi
DY
Institute of Biomedical Science and Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-Dong, Sungdong-Ku, Seoul 133-791, Korea.
Park
Shin-Young
SY
Cho
Ju Hwan
JH
Lee
Ki Sung
KS
Min
Do Sik
do S
Han
Joong-Soo
JS
D000818:Animals; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004789:Enzyme Activation; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry; D016501:Neurites / Q000187:drug effects*; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D051966:Phospholipase C gamma / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D051381:Rats; D014162:Transfection; D018631:ras Proteins / Q000502:physiology*; D019061:src-Family Kinases / Q000502:physiology*
D016222:Fibroblast Growth Factor 2; D019061:src-Family Kinases; D051966:Phospholipase C gamma; D010739:Phospholipase D; C106801:phospholipase D1; D018631:ras Proteins