Relationship between phosphatidic acid level and regulation of protein transit in colonic epithelial cell line HT29-cl19A

作     者：Auger, R Robin, P Camier, B Vial, G Rossignol, B Tenu, JP Raymond, MN 

作者机构：Univ Paris 11 CNRS UMR 8619 Lab Biochim Transports Cellulaires F-91405 Orsay France 

出 版 物：《JOURNAL OF BIOLOGICAL CHEMISTRY》 (生物化学杂志)

年 卷 期：1999年第274卷第40期

页      面：28652-28659页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

主　　题：卡巴胆碱/药理学 结肠/细胞学 结肠/代谢 二酰甘油激酶/代谢 酶激活 酶激动剂类/药理学 酶联免疫吸附测定 上皮细胞/代谢 高尔基体/代谢 HT29细胞 动力学 磷脂酸类/代谢 磷脂酶D/代谢 C型磷脂酶类/代谢 α1抗胰蛋白酶/代谢 人类 

摘      要：Colonic epithelial HT29-cl19A cells are polarized and secrete proteins among which alpha(1)-antitrypsin represents about 95%. Secretion occurs via a constitutive pathway, so that the rates of secretion directly reflect the rates of protein transit. In this paper we have demonstrated that: 1) in resting cells phospholipase D (PLD) is implicated in the control of apical protein transit;2) phorbol esters stimulate apical protein transit (stimulation factor 2.2), which is correlated with a PLD-catalyzed production of phosphatidic acid (PA) (2.45-fold increase);3) the stimulation of cholinergic receptors by carbachol results in an increase (stimulation factor 1.45) of apical protein transit which is independent of protein kinase C and PLD activities, but related to PA formation (1.7-fold increase) via phospholipase(s) C and diacylglycerol kinase activation;4) an elevation of the cAMP level enhances apical protein transit by a PA-independent mechanism;5) a trans-Golgis network or post-trans-Golgi network step of the transit is the target for the regulatory events. In conclusion, we have shown that PA can be produced by two independent signaling pathways;whatever the pathway followed, a close relationship between the amount of PA and the level of secretion was observed.