Ca2+-mediated activation of ERK in hepatocytes by norepinephrine and prostaglandin F2 alpha: role of calmodulin and Src kinases.
Ca2+-mediated activation of ERK in hepatocytes by norepinephrine and prostaglandin F2 alpha: role of calmodulin and Src kinases.
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去甲肾上腺素和前列腺素 F2 α 在肝细胞中 Ca2+ 介导的 ERK 激活：钙调蛋白和 Src 激酶的作用。
DOI：
10.1186/1471-2121-3-5
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Christoffersen T
中科院分区：
文献类型：
--
作者：
Melien O;Nilssen LS;Dajani OF;Sand KL;Iversen JG;Sandnes DL;Christoffersen T
以往的研究表明，几种激活七螺旋G蛋白偶联受体的药物可以激活肝细胞中的细胞外信号调节激酶ERK1(P44mapk)和ERK2(P42mapk)。将它们的信号传递到ERK1/2的分子通路只有部分被阐明。在本研究中，我们探讨了去甲肾上腺素和前列腺素(PG)F2α诱导ERK1/2激活的钙和钙依赖步骤的作用。用钙离子螯合剂BAPTA-AM或EGTA以及钙离子内流阻滞剂Gd处理细胞后，ERK反应部分降低。此外，钙调素拮抗剂W-7、三氟拉嗪和J-8显著抑制ERK的激活。多功能钙/钙调素依赖性蛋白激酶抑制剂KN-93对ERK的激活无影响。Src激酶抑制剂Pp1和Pp2可部分抑制去甲肾上腺素和PgF2α引起的ERK反应。这些结果表明，钙离子参与了激素对肝细胞G蛋白偶联受体诱导的ERK激活，并提示钙调素和Src激酶可能在这些信号通路中发挥作用。
Previous studies have shown that several agents that stimulate heptahelical G-protein coupled receptors activate the extracellular signal regulated kinases ERK1 (p44mapk) and ERK2 (p42mapk) in hepatocytes. The molecular pathways that convey their signals to ERK1/2 are only partially clarified. In the present study we have explored the role of Ca2+ and Ca2+-dependent steps leading to ERK1/2 activation induced by norepinephrine and prostaglandin (PG)F2α. Pretreatment of the cells with the Ca2+ chelators BAPTA-AM or EGTA, as well as the Ca2+ influx inhibitor gadolinium, resulted in a partial decrease of the ERK response. Furthermore, the calmodulin antagonists W-7, trifluoperazine, and J-8 markedly decreased ERK activation. Pretreatment with KN-93, an inhibitor of the multifunctional Ca2+/calmodulin-dependent protein kinase, had no effect on ERK activation. The Src kinase inhibitors PP1 and PP2 partially diminished the ERK responses elicited by both norepinephrine and PGF2α. The present data indicate that Ca2+ is involved in ERK activation induced by hormones acting on G protein-coupled receptors in hepatocytes, and suggest that calmodulin and Src kinases might play a role in these signaling pathways.
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DOI：
10.1111/j.1432-1033.1984.tb07904.x
发表时间：
1984-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
CHRISTOFFERSEN, T;REFSNES, M;SONNE, O
通讯作者：
SONNE, O
影响因子：
11.4
作者：
Daub, H;Wallasch, C;Ullrich, A
通讯作者：
Ullrich, A
影响因子：
8.3
作者：
Eguchi, S;Iwasaki, H;Hirata, Y
通讯作者：
Hirata, Y
DOI：
10.1152/ajpgi.1997.272.6.g1425
发表时间：
1997-06-01
影响因子：
4.5
作者：
Benzeroual, K;VandeWerve, G;Haddad, P
通讯作者：
Haddad, P
影响因子：
3.6
作者：
Berts, A;Zhong, HY;Minneman, KP
通讯作者：
Minneman, KP