钙在C2C12成肌细胞中鞘氨醇-1-磷酸诱导的磷脂酶D活性中的作用。

A role for calcium in sphingosine 1-phosphate-induced phospholipase D activity in C2C12 myoblasts.

作者信息

Meacci Elisabetta, Becciolini Laura, Nuti Francesca, Donati Chiara, Cencetti Francesca, Farnararo Marta, Bruni Paola

机构信息

Dipartimento di Scienze Biochimiche, Università di Firenze, Viale G.B. Morgagni 50, 50134 Firenze, Italy.

出版信息

FEBS Lett. 2002 Jun 19;521(1-3):200-4. doi: 10.1016/s0014-5793(02)02866-1.

DOI:10.1016/s0014-5793(02)02866-1

PMID:12067705

Abstract

Receptor-regulated phospholipase D (PLD) is a key signaling pathway implicated in the control of fundamental biological processes. Here evidence is presented that in addition to protein kinase C (PKC) and Rho GTPases, Ca(2+) response evoked by sphingosine 1-phosphate (S1P) also participates to the enzyme regulation. Ca(2+) was found critical for PKC(alpha)-mediated PLD activation. Moreover, S1P-induced PLD activity resulted diminished by calmodulin inhibitors such as W-7 and CGS9343B implicating its involvement in the process. A plausible candidate for Ca(2+)-dependent PLD regulation by S1P was represented by calcineurin, in view of the observed reduction of the stimulatory effect by cyclosporin A. In contrast, monomeric GTP-binding protein Ral was translocated to membranes by S1P in a Ca(2+)-independent manner, ruling out its possible role in agonist-mediated regulation of PLD.

摘要

受体调节型磷脂酶D（PLD）是参与控制基本生物学过程的关键信号通路。本文提供的证据表明，除蛋白激酶C（PKC）和Rho GTP酶外，1-磷酸鞘氨醇（S1P）引发的Ca(2+)反应也参与该酶的调节。发现Ca(2+)对PKC(α)介导的PLD激活至关重要。此外，诸如W-7和CGS9343B等钙调蛋白抑制剂使S1P诱导的PLD活性降低，这表明其参与了该过程。鉴于观察到环孢菌素A可降低刺激作用，钙调神经磷酸酶可能是S1P对Ca(2+)依赖性PLD调节的一个合理候选者。相反，单体GTP结合蛋白Ral以不依赖Ca(2+)的方式被S1P转运至细胞膜，排除了其在激动剂介导的PLD调节中的可能作用。