Rap1 is involved in cell stretching modulation of p38 but not ERK or JNK MAP kinase.
Rap1 is involved in cell stretching modulation of p38 but not ERK or JNK MAP kinase.
复制标题
Rap1 参与 p38 的细胞拉伸调节，但不参与 ERK 或 JNK MAP 激酶。
作者：
Y. Sawada;Kozo Nakamura;Koichi Doi;K. Takeda;K. Tobiume;M. Saitoh;Keiichi Morita;I. Komuro;K. D. Vos;M. Sheetz;H. Ichijo
机械力或机械应力调节细胞内信号通路，包括丝裂原激活蛋白激酶（MAP 激酶）级联。在我们的系统中，细胞拉伸激活而细胞收缩失活所有三种 MAP 激酶途径（MKK1/2-细胞外信号调节激酶 (ERK)、MKK4 (SEK1)-cJun N 末端激酶 (JNK) 和 MKK3/6-p38 途径）。然而，人们对将机械力与 MAP 激酶级联联系起来的分子机制知之甚少。为了测试 Ras 和 Rap1 是否是拉伸激活的 MAP 激酶途径中可能的组成部分，我们检查了 Ras 和 Rap1 是否被细胞拉伸激活，以及抑制它们的活性是否会降低拉伸增强的 MAP 激酶活性。 Rap1通过细胞拉伸激活并通过细胞收缩失活，而Ras通过细胞拉伸失活并通过细胞收缩激活。 Rap1GapII 和 SPA-1 是 Rap1 活性的下调因子，可降低拉伸增强的 p38 活性，而 Ras 的显性失活突变体 (RasN17) 不会抑制拉伸引发的 MAP 激酶激活。此外，Rap1 的过表达增强了 p38 活性，但不增强 ERK 或 JNK 活性。这些结果表明 Rap1 参与将拉伸起始信号转导至 MKK3/6-p38 通路，但不转导至 MEK1/2-ERK 或 MKK4 (SEK1)/MKK7-JNK 通路。因此，Rap1 在力启动的信号转导中发挥着独特的作用。
Mechanical force or mechanical stress modulates intracellular signal pathways, including the mitogen-activated protein kinase (MAP kinase) cascades. In our system, cell stretching activated and cell contraction inactivated all three MAP kinase pathways (MKK1/2-extracellular signal-regulated kinase (ERK), MKK4 (SEK1)-cJun N-terminal kinase (JNK) and MKK3/6-p38 pathways). However, little is known about the molecular mechanisms that link the mechanical force to the MAP kinase cascades. To test whether Ras and Rap1 are possible components in the stretch-activated MAP kinase pathways, we examined if Ras and Rap1 were activated by cell stretching and if inhibition of their activity decreased the stretch-enhanced MAP kinase activity. Rap1 was activated by cell stretching and inactivated by cell contraction, whereas Ras was inactivated by cell stretching and activated by cell contraction. Rap1GapII and SPA-1, downregulators of Rap1 activity, decreased the stretch-enhanced p38 activity, whereas a dominant-negative mutant of Ras (RasN17) did not inhibit the stretch-initiated activation of MAP kinases. Furthermore, overexpression of Rap1 enhanced p38 activity but not ERK or JNK activity. These results indicate that Rap1 is involved in transducing the stretch-initiated signal to the MKK3/6-p38 pathway, but not to the MEK1/2-ERK or the MKK4 (SEK1)/MKK7-JNK pathway. Thus, Rap1 plays a unique role in force-initiated signal transduction.
DOI：
--
发表时间：
2000
期刊：
--
影响因子：
--
作者：
R. Pankov;E. Cukierman;B. Katz;Kazue Matsumoto;D. C. Lin;Shin Lin;Cornelia S. Hahn;Kenneth M. Yamada
通讯作者：
R. Pankov;E. Cukierman;B. Katz;Kazue Matsumoto;D. C. Lin;Shin Lin;Cornelia S. Hahn;Kenneth M. Yamada
影响因子：
3.7
作者：
Lee, DJ;Rosenfeldt, H;Grinnell, F
通讯作者：
Grinnell, F