Distinct kinases are involved in contraction of cat esophageal and lower esophageal sphincter smooth muscles.

Distinct kinases are involved in contraction of cat esophageal and lower esophageal sphincter smooth muscles.
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不同的激酶参与猫食管和下食管括约肌平滑肌的收缩。

DOI:
10.1152/ajpcell.00390.2003
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发表时间:
2004
期刊:
American journal of physiology. Cell physiology
影响因子:
--
通讯作者:
Biancani,Piero
Biancani,Piero
中科院分区:
--
文献类型:
--
作者:
Kim,Nayoung;Cao,Weibiao;Song,InSung;Kim,ChungYong;Harnett,KarenM;Cheng,Ling;Walsh,MichaelP;Biancani,Piero

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平滑肌的收缩取决于肌球蛋白轻链激酶(MLCK)和肌球蛋白轻链磷酸酶(MLCP)活性的平衡。由于 MLCK 激活取决于钙调蛋白的激活,而钙调蛋白需要高 Ca2+ 浓度,因此磷酸酶抑制已被用来解释低胞质 Ca2+ 水平下的收缩。在食管 (ESO) 中观察到的 Ca2+ 独立蛋白激酶 Cε (PKCε) 的激活与 MLC 磷酸化之间的联系(Sohn UD、Cao W、Tang DC、Stull JT、Haeberle JR、Wang CLA、Harnett KM、Behar J 和 Biancani P.Am J Physiol Gastrointest Liver Physiol281: G467–G478, 2001),然而,尚未得到阐明。我们使用磷酸酶和激酶抑制剂以及信号酶抗体与来自 ESO 和下食管括约肌 (LES) 的完整且皂苷通透的分离平滑肌细胞相结合,以检查 ESO 中 PKCε 依赖性、Ca2+ 独立的信号传导。磷酸酶抑制剂冈田酸和微囊藻毒素-LR,以及针对 1 型蛋白丝氨酸/苏氨酸磷酸酶催化亚基的抗体,在 ESO 和 LES 中引起类似的收缩。 MLCK 抑制剂(ML-7、ML-9 和 SM-1)和 MLCK 抗体可抑制 LES 中由磷酸酶抑制引起的收缩,但在 ESO 中则不然。 PKC 抑制剂白屈菜红碱和 PKCε 抗体(但不是 PKCβII 抗体)抑制 ESO 收缩,但不抑制 LES 收缩。在 ESO 中,大田酸触发 PKCε 从胞质部分转移到颗粒部分,并增加整合素连接激酶 (ILK) 的活性。丝裂原激活蛋白 (MAP) 激酶 ERK1/ERK2 和 ILK 抗体以及 MAP 激酶激酶 (MEK) 抑制剂 PD-98059 可抑制冈田酸诱导的 ILK 活性和 ESO 收缩。我们得出的结论是,磷酸酶抑制增强了 MLCK 在 LES 中的作用,但在 ESO 中则不然。 ESO 的收缩是由 PKCε、MEK、ERK1/2 和 ILK 的激活介导的。
Contraction of smooth muscle depends on the balance of myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP) activities. Because MLCK activation depends on the activation of calmodulin, which requires a high Ca2+concentration, phosphatase inhibition has been invoked to explain contraction at low cytosolic Ca2+levels. The link between activation of the Ca2+-independent protein kinase Cε (PKCε) and MLC phosphorylation observed in the esophagus (ESO) (Sohn UD, Cao W, Tang DC, Stull JT, Haeberle JR, Wang CLA, Harnett KM, Behar J, and Biancani P.Am J Physiol Gastrointest Liver Physiol281: G467–G478, 2001), however, has not been elucidated. We used phosphatase and kinase inhibitors and antibodies to signaling enzymes in combination with intact and saponin-permeabilized isolated smooth muscle cells from ESO and lower esophageal sphincter (LES) to examine PKCε-dependent, Ca2+-independent signaling in ESO. The phosphatase inhibitors okadaic acid and microcystin-LR, as well as an antibody to the catalytic subunit of type 1 protein serine/threonine phosphatase, elicited similar contractions in ESO and LES. MLCK inhibitors (ML-7, ML-9, and SM-1) and antibodies to MLCK inhibited contraction induced by phosphatase inhibition in LES but not in ESO. The PKC inhibitor chelerythrine and antibodies to PKCε, but not antibodies to PKCβII, inhibited contraction of ESO but not of LES. In ESO, okadaic acid triggered translocation of PKCε from cytosolic to particulate fraction and increased activity of integrin-linked kinase (ILK). Antibodies to the mitogen-activated protein (MAP) kinases ERK1/ERK2 and to ILK, and the MAP kinase kinase (MEK) inhibitor PD-98059, inhibited okadaic acid-induced ILK activity and contraction of ESO. We conclude that phosphatase inhibition potentiates the effects of MLCK in LES but not in ESO. Contraction of ESO is mediated by activation of PKCε, MEK, ERK1/2, and ILK.
LES 和食管平滑肌的肌球蛋白轻链激酶和 PKC 依赖性收缩。
DOI: 10.1152/ajpgi.2001.281.2.g467
发表时间: 2001
期刊: American journal of physiology. Gastrointestinal and liver physiology.
影响因子: --
作者:
Sohn,UD;Cao,W;Tang,DC;Stull,JT;Haeberle,JR;Wang,CL;Harnett,KM;Behar,J;Biancani,P
通讯作者: Biancani,P
由不同 PKC 同工酶介导的激动剂、生长因子和 Ca(2) 诱导的持续肌肉收缩。
DOI: 10.1152/ajpgi.2000.279.1.g201
发表时间: 2000
期刊: American journal of physiology. Gastrointestinal and liver physiology
影响因子: --
作者:
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发表时间: 1997-05-01
影响因子: 6.4
作者:
Whelchel, A;Evans, J;Posada, J
通讯作者: Posada, J
DOI: 10.1038/40187
发表时间: 1997-10-30
期刊: NATURE
影响因子: 64.8
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C(2)-神经酰胺诱导的圆形平滑肌细胞收缩涉及猫食道中的 PKC-epsilon 和 p44/p42 MAPK 激活。
DOI: --
发表时间: 2002
影响因子: 4.8
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