Phospholipase D1 activation through Src and Ras is involved in basic fibroblast growth factor-induced neurite outgrowth of H19-7 cells

被引:19
|
作者
Oh, Doo-Yi
Park, Shin-Young
Cho, Ju Hwan
Lee, Ki Sung
Min, Do Sik
Han, Joong-Soo
机构
[1] Hanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea
[2] Hanyang Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 133791, South Korea
[3] PaiChai Univ, Res Ctr Biomed Resources, Taejon 302735, South Korea
[4] Pusan Natl Univ, Coll Nat Sci, Dept Mol Biol, Pusan 609735, South Korea
关键词
phospholipase D1 (PLD1); neurite outgrowth; basic fibroblast growth factor (bFGF); Src; Ras; phospholipase; C-gamma (PLC-gamma);
D O I
10.1002/jcb.21166
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:221 / 234
页数:14
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