Regulation of basal LC20 phosphorylation by MYPT1 and CPI-17 in murine gastric antrum, gastric fundus, and proximal colon smooth muscles.
Regulation of basal LC20 phosphorylation by MYPT1 and CPI-17 in murine gastric antrum, gastric fundus, and proximal colon smooth muscles.
复制标题
DOI：
10.1111/j.1365-2982.2011.01769.x
复制
发表时间：
2011-10
影响因子：
3.5
通讯作者：
Perrino BA
中科院分区：
文献类型：
--
作者：
Bhetwal BP;An CL;Fisher SA;Perrino BA
肌球蛋白轻链激酶(MLCK)和磷酸酶(MLCP)控制着肌球蛋白轻链(LC20)的磷酸化和平滑肌收缩。Rho激酶(ROK)抑制MLCP，导致在给定的[Ca~(2+)]i时更大的LC_(20)磷酸化和力的产生。在这里，我们研究了韩国在调节胃底、胃窦和近端结肠平滑肌的LC_(20)磷酸化和自发收缩中的作用。蛋白质和磷酸化水平用免疫印迹法检测。检测Y27632、尼卡地平和GF109203X对磷酸化水平和收缩的影响。γ-肌动蛋白在三种肌肉中的表达相似。在胃窦和近端结肠平滑肌中，LC_(20)和PS_(19)最高，ROK1和ROK2最低。LZ+/−MYPT1、CPI-17和pT696、pT853、pT38在胃底和近端结肠平滑肌中表达最高。M-RIP在胃底表达最低，在胃窦和近端结肠平滑肌表达最高。Y27632使各肌层的pT853降低，但仅降低眼底肌层的pT696。尼卡地平对各段结肠和胃底的pT38无影响，GF109203X可降低近端结肠和胃底的pT38。Y27632或尼卡地平可降低近端结肠和眼底平滑肌的PS19。Y27632或尼卡地平抑制胃窦和近端结肠平滑肌的自发收缩，但仅Y27632降低眼底平滑肌张力。无外钙使每条血管松弛，并取消LC_(20)磷酸化。涉及MLCP相互作用蛋白LZ+/−MYPT1、M-RIP和CPI-17的器官特异性机制对调节胃肠道(GI)平滑肌的基础LC_(20)磷酸化至关重要。
Myosin light chain kinase (MLCK) and phosphatase (MLCP) govern myosin light chain (LC20) phosphorylation and smooth muscle contraction. Rho kinase (ROK) inhibits MLCP, resulting in greater LC20 phosphorylation and force generation at a given [Ca2+]i. Here, we investigate the role of ROK in regulating LC20 phosphorylation and spontaneous contractions of gastric fundus, gastric antrum, and proximal colon smooth muscles. Protein and phosphorylation levels were determined by western blotting. The effects of Y27632, nicardipine, and GF109203X on phosphorylation levels and contraction were measured. γ-Actin expression is similar in all three smooth muscles. LC20 and pS19 are highest, but ROK1 and ROK2 are lowest, in antrum and proximal colon smooth muscles. LZ+/− MYPT1, CPI-17, and pT696, pT853, and pT38 are highest in fundus and proximal colon smooth muscles. M-RIP expression is lowest in fundus, and highest in antrum and proximal colon smooth muscles. Y27632 reduced pT853 in each smooth muscle, but reduced pT696 only in fundus smooth muscles. Nicardipine had no effect on pT38 in each smooth muscle, while GF109203X reduced pT38 in proximal colon and fundus smooth muscles. Y27632 or nicardipine reduced pS19 in proximal colon and fundus smooth muscles. Y27632 or nicardipine inhibited antrum and proximal colon smooth muscle spontaneous contractions, but only Y27632 reduced fundus smooth muscle tone. Zero external Ca2+ relaxed each smooth muscle and abolished LC20 phosphorylation. Organ-specific mechanisms involving the MLCP interacting proteins LZ+/− MYPT1, M-RIP, and CPI-17 are critical to regulating basal LC20 phosphorylation in gastrointestinal (GI) smooth muscles.
登录
查看更多内容
影响因子：
3.5
作者：
Murányi, A;Derkach, D;Hartshorne, DJ
通讯作者：
Hartshorne, DJ
影响因子：
5
作者：
Payne, MC;Zhang, HY;Fisher, SA
通讯作者：
Fisher, SA
影响因子：
7.3
作者：
Depoortere, Inge;Thijs, Theo;Tack, Jan
通讯作者：
Tack, Jan
影响因子：
7.3
作者：
Alvarez, S. M.;Miner, A. S.;Ratz, P. H.
通讯作者：
Ratz, P. H.
影响因子：
3.6
作者：
Ihara, Eikichi;Beck, Paul L.;MacDonald, Justin A.
通讯作者：
MacDonald, Justin A.