Thodeti Charles Kumar, Sjölander Anita
Department of Laboratory Medicine, Division of Experimental Pathology, Lund University, University Hospital Malmö, Malmö-S 205 02, Sweden.
Adv Exp Med Biol. 2002;507:187-91. doi: 10.1007/978-1-4615-0193-0_29.
LTD4 induces a calcium signal that consists of a mobilization from internal stores regulated by PTX-insensitive G protein, Rho, and, an influx across the plasma membrane regulated by PTX-sensitive Gi protein in human intestinal epithelial cells. The LTD4 induced mobilization of Ca2+ is mediated by a PH domain dependent association between PLC-gamma 1 and G beta gamma subunits. This interaction requires Src kinase activity as well as the association of this kinase with PLC-gamma 1, suggesting a G beta gamma mediated recruitment of proteins to the plasma membrane and formation of a signaling complex which is essential for the downstream Ca2+ signal. We found a cAMP-dependent protein kinase activity upstream of tyrosine kinase(s) and downstream of Gi protein, that is essential for LTD4-induced Ca2+ influx. This model of the LTD4-induced Ca2+ signaling pathways in intestinal epithelial cells is outlined schematically in Fig. 1.
白三烯D4（LTD4）在人肠上皮细胞中诱导产生一种钙信号，该信号包括由百日咳毒素（PTX）不敏感的G蛋白Rho调节的从内部储存库释放钙，以及由PTX敏感的Gi蛋白调节的跨质膜的钙流入。LTD4诱导的Ca2+释放是由磷脂酶Cγ1（PLC-γ1）与Gβγ亚基之间依赖于PH结构域的结合介导的。这种相互作用需要Src激酶活性以及该激酶与PLC-γ1的结合，这表明Gβγ介导蛋白质募集到质膜并形成信号复合物，这对于下游Ca2+信号至关重要。我们发现一种依赖于环磷酸腺苷（cAMP）的蛋白激酶活性位于酪氨酸激酶上游和Gi蛋白下游，这对于LTD4诱导的Ca2+内流至关重要。图1示意性地概述了肠上皮细胞中LTD4诱导的Ca2+信号通路模型。
