Modulation of Ca2+ mobilization by protein kinase C in the submandibular duct cell line A253.
Modulation of Ca2+ mobilization by protein kinase C in the submandibular duct cell line A253.
复制标题
下颌下导管细胞系 A253 中蛋白激酶 C 对 Ca2 动员的调节。
DOI：
10.1023/a:1006925408055
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发表时间：
1999
影响因子：
4.3
通讯作者：
Martinez,JR
中科院分区：
文献类型：
--
作者：
Sugita,K;Mörk,AC;Zhang,GH;Martinez,JR
研究了蛋白激酶C（PKC）亚型在人颌下腺导管细胞系A253中的表达及其对Ca ~（2+）动员的调节作用。在该细胞系中表达三种新的PKC（nPKC）亚型（δ、ε和θ）和一种非典型PKC（aPKC）亚型（λ）。不存在经典的PKC（cPKC）亚型。研究了PKC激活剂佛波醇12-肉豆蔻酸酯-13-乙酸酯（PMA）和PKC抑制剂钙磷蛋白C（CC）和双吲哚马来酰亚胺I（BSM）对三磷酸肌醇（IP 3）和钙离子对ATP和毒胡萝卜素（TG）反应的影响。PMA预处理抑制ATP诱导的IP 3形成、Ca ~（2+）释放和Ca ~（2+）内流。CC或BSM预处理可轻度促进IP 3的形成，但抑制ATP诱导的Ca 2+释放和Ca 2+内流。与此相反，PMA预暴露并没有修改由TG诱导的Ca 2+释放，但减少了这种Ca 2 +-ATP酶抑制剂存在下观察到的Ca 2+内流。这些结果表明，PKC通过（1）抑制磷脂酰肌醇周转和改变Ca ~（2+）通道对IP ~ 3的敏感性，（2）改变TG敏感性Ca ~（2+）ATP酶的活性、对抑制剂的敏感性或分布，以及（3）调节Ca ~（2+）内流途径来调节A253细胞IP ~ 3/Ca ~（2+）信号转导通路的元件。
The expression of protein kinase C (PKC) isoforms and the modulation of Ca2+mobilization by PKC were investigated in the human submandibular duct cell line A253. Three new PKC (nPKC) isoforms (δ, ε, and θ) and one atypical PKC (aPKC) isoform (λ) are expressed in this cell line. No classical PKC (cPKC) isoforms were present. The effects of the PKC activator phorbol 12-myristate-13-acetate (PMA) and of the PKC inhibitors calphostin C (CC) and bisindolymaleimide I (BSM) on inositol 1,4,5-trisphosphate (IP3) and Ca2+responses to ATP and to thapsigargin (TG) were investigated. Pre-exposure to PMA inhibited IP3formation, Ca2+release and Ca2+influx in response to ATP. Pre-exposure to CC or BSM slightly enhanced IP3formation but inhibited the Ca2+release and the Ca2+influx induced by ATP. In contrast, pre-exposure to PMA did not modify the Ca2+release induced by TG, but reduced the influx of Ca2+seen in the presence of this Ca2+-ATPase inhibitor. These results suggest that PKC modulates elements of the IP3/Ca2+signal transduction pathway in A253 cells by (1) inhibiting phosphatidylinositol turnover and altering the sensitivity of the Ca2+channels to IP3, (2) altering the activity, the sensitivity to inhibitors, or the distribution of the TG-sensitive Ca2+ATPase, and (3) modulating Ca2+entry pathways.