Essential role of PI3-kinase and phospholipase A2 in Dictyostelium discoideum chemotaxis.
Essential role of PI3-kinase and phospholipase A2 in Dictyostelium discoideum chemotaxis.
复制标题
DOI：
10.1083/jcb.200701134
复制
发表时间：
2007-06-04
期刊：
影响因子：
--
通讯作者：
Kortholt A
中科院分区：
文献类型：
--
作者：
van Haastert PJ;Keizer-Gunnink I;Kortholt A
检测了不同浓度环磷酸腺苷(CAMP)对特定基因缺失和药物抑制第二信使系统PI3-激酶、磷脂酶C(PLC)、磷脂酶A2(PLA2)和胞内钙离子的一种或全部组合的趋化作用。结果表明，抑制PI3-激酶或PLA2均可抑制浅cAMP梯度中的趋化作用，但必须同时抑制这两种酶才能阻止cAMP梯度较大时的趋化作用，提示PI3-K和PLA2是趋化作用的两个多余介质。缺乏PLC活性的突变细胞具有正常的趋化作用；然而，额外的PLA2抑制完全阻断了趋化作用，而抑制PI3-激酶则不起作用，这表明PLC缺失细胞的所有趋化作用都是由PLA2介导的。IP3受体缺失的细胞具有相反的表型：趋化性完全依赖于PI3-激酶，对PLA2抑制剂不敏感。这表明，PI3-激酶介导的趋化作用受PLC调控，可能是通过控制PIP2水平和磷酸酶及张力蛋白同源酶(PTEN)活性，而PLA2介导的趋化作用似乎是由细胞内钙离子控制的。
Chemotaxis toward different cyclic adenosine monophosphate (cAMP) concentrations was tested in Dictyostelium discoideum cell lines with deletion of specific genes together with drugs to inhibit one or all combinations of the second-messenger systems PI3-kinase, phospholipase C (PLC), phospholipase A2 (PLA2), and cytosolic Ca2+. The results show that inhibition of either PI3-kinase or PLA2 inhibits chemotaxis in shallow cAMP gradients, whereas both enzymes must be inhibited to prevent chemotaxis in steep cAMP gradients, suggesting that PI3-kinase and PLA2 are two redundant mediators of chemotaxis. Mutant cells lacking PLC activity have normal chemotaxis; however, additional inhibition of PLA2 completely blocks chemotaxis, whereas inhibition of PI3-kinase has no effect, suggesting that all chemotaxis in plc-null cells is mediated by PLA2. Cells with deletion of the IP3 receptor have the opposite phenotype: chemotaxis is completely dependent on PI3-kinase and insensitive to PLA2 inhibitors. This suggest that PI3-kinase–mediated chemotaxis is regulated by PLC, probably through controlling PIP2 levels and phosphatase and tensin homologue (PTEN) activity, whereas chemotaxis mediated by PLA2 appears to be controlled by intracellular Ca2+.
登录
查看更多内容
影响因子：
3.3
作者：
Seastone, DJ;Zhang, LY;Cardelli, J
通讯作者：
Cardelli, J
DOI：
10.1007/bf01896891
发表时间：
1970-01-01
期刊：
EXPERIENTIA
影响因子：
--
作者：
KONIJN, TM
通讯作者：
KONIJN, TM
影响因子：
11.4
作者：
Traynor, D;Milne, JLS;Kay, RR
通讯作者：
Kay, RR
影响因子：
64.8
作者：
Baggiolini, M
通讯作者：
Baggiolini, M
影响因子：
7.7
作者：
Postma, M;Bosgraaf, L;Van Haastert, PJM
通讯作者：
Van Haastert, PJM