The pro-apoptotic protein Par-4 facilitates vascular contractility by cytoskeletal targeting of ZIPK.
The pro-apoptotic protein Par-4 facilitates vascular contractility by cytoskeletal targeting of ZIPK.
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DOI：
10.1111/j.1582-4934.2008.00374.x
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发表时间：
2009-05
影响因子：
5.3
通讯作者：
Morgan KG
中科院分区：
文献类型：
--
作者：
Vetterkind S;Morgan KG
PAR-4(前列腺凋亡反应4)是一种促凋亡蛋白和肿瘤抑制因子，最初被认为是一种在前列腺癌细胞凋亡过程中上调的基因产物。在这里，我们第一次显示，PAR-4在血管平滑肌中表达，并与肌动蛋白细丝束共存。此外，我们证明了ZIPK的靶向肌动蛋白细丝，如观察到的前列腺素F-2α刺激，是抑制存在细胞意味着PAR-4诱骗肽。同样的诱饵多肽也能显著抑制前列腺素F-2α引起的平滑肌组织收缩。此外，使用反义吗啉核苷酸敲除PAR-4导致显著降低收缩能力，肌球蛋白轻链和肌球蛋白磷酸酶靶向亚单位磷酸化。这些结果表明，PAR-4通过将ZIPK靶向位于肌动蛋白细丝上的底物肌球蛋白轻链和MYPT附近来促进收缩。这些结果证实PAR-4是分化的、收缩的血管平滑肌中肌球蛋白轻链磷酸化的一种新的调节因子。
Par-4 (prostate apoptosis response 4) is a pro-apoptotic protein and tumour suppressor that was originally identified as a gene product up-regulated during apoptosis in prostate cancer cells. Here, we show, for the first time, that Par-4 is expressed and co-localizes with the actin filament bundles in vascular smooth muscle. Furthermore, we demonstrate that targeting of ZIPK to the actin filaments, as observed upon PGF-2α stimulation, is inhibited by the presence of a cell permeant Par-4 decoy peptide. The same decoy peptide also significantly inhibits PGF-2α induced contractions of smooth muscle tissue. Moreover, knockdown of Par-4 using antisense morpholino nucleotides results in significantly reduced contractility, and myosin light chain and myosin phosphatase target subunit phosphorylation. These results indicate that Par-4 facilitates contraction by targeting ZIPK to the vicinity of its substrates, myosin light chain and MYPT, which are located on the actin filaments. These results identify Par-4 as a novel regulator of myosin light chain phosphorylation in differentiated, contractile vascular smooth muscle.
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影响因子：
2.5
作者：
Cavagna, P;Menotti, A;Stanyon, R
通讯作者：
Stanyon, R
影响因子：
5.5
作者：
Je, HD;Gangopadhyay, SS;Morgan, KG
通讯作者：
Morgan, KG
影响因子：
3.3
作者：
Mulder, J;Ariaens, A;Moolenaar, WH
通讯作者：
Moolenaar, WH
影响因子：
82.9
作者：
Guo, Q;Fu, WM;Mattson, MP
通讯作者：
Mattson, MP
Rho-kinase in Vivo的肌球蛋白磷酸酶的肌球蛋白结合亚基（MB）的磷酸化。
DOI：
10.1083/jcb.147.5.1023
发表时间：
1999-11-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kawano Y;Fukata Y;Oshiro N;Amano M;Nakamura T;Ito M;Matsumura F;Inagaki M;Kaibuchi K
通讯作者：
Kaibuchi K