Rac1 links integrin-mediated adhesion to the control of lactational differentiation in mammary epithelia.
Rac1 links integrin-mediated adhesion to the control of lactational differentiation in mammary epithelia.
复制标题
RAC1将整合素介导的粘附连接到控制乳腺上皮中泌乳分化的粘附。
DOI：
10.1083/jcb.200601059
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发表时间：
2006-06-05
期刊：
影响因子：
--
通讯作者：
Streuli CH
中科院分区：
文献类型：
--
作者：
Akhtar N;Streuli CH
乳腺分化过程中组织特异性基因的表达依赖于两个不同信号事件的巧合：β1整合素与细胞外基质（ECM）的持续接合和催乳素（Prl）的激素刺激。整合素和Prl受体（PrlR）系统如何整合以调节乳蛋白基因合成尚不清楚。在这项研究中，我们确定Rac 1作为一个关键环节。显性阴性Rac 1阻止在基底膜上作为三维腺泡培养的原代乳腺上皮细胞中PRL诱导的乳蛋白β-酪蛋白的合成。相反，活化的Rac 1挽救了在通常不允许乳腺分化的条件下发生的β-酪蛋白合成缺陷，无论是在β1整合素缺失细胞中还是在胶原蛋白上培养的野生型细胞中。Rac 1是整合素下游激活PrlR/Stat 5信号级联所必需的。Cdc 42也是乳蛋白合成所必需的，但通过与Rac 1不同的机制发挥作用。这项研究确定了整合ECM和激素提供的信号作为Rho家族鸟苷三磷酸酶的新作用。
The expression of tissue-specific genes during mammary gland differentiation relies on the coincidence of two distinct signaling events: the continued engagement of β1 integrins with the extracellular matrix (ECM) and a hormonal stimulus from prolactin (Prl). How the integrin and Prl receptor (PrlR) systems integrate to regulate milk protein gene synthesis is unknown. In this study, we identify Rac1 as a key link. Dominant-negative Rac1 prevents Prl-induced synthesis of the milk protein β-casein in primary mammary epithelial cells cultured as three-dimensional acini on basement membrane. Conversely, activated Rac1 rescues the defective β-casein synthesis that occurs under conditions not normally permissive for mammary differentiation, either in β1 integrin–null cells or in wild-type cells cultured on collagen. Rac1 is required downstream of integrins for activation of the PrlR/Stat5 signaling cascade. Cdc42 is also necessary for milk protein synthesis but functions via a distinct mechanism to Rac1. This study identifies the integration of signals provided by ECM and hormones as a novel role for Rho family guanosine triphosphatases.
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影响因子：
2.6
作者：
Boussadia, O;Kutsch, S;Kemler, R
通讯作者：
Kemler, R
影响因子：
64.8
作者：
Radisky, DC;Levy, DD;Bissell, MJ
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影响因子：
11.4
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Knebel, A;Rahmsdorf, HJ;Herrlich, P
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影响因子：
7.8
作者：
Naylor, Matthew J;Li, Na;Cheung, Julia;Lowe, Emma T;Lambert, Elise;Marlow, Rebecca;Wang, Pengbo;Schatzmann, Franziska;Wintermantel, Timothy;Schuetz, Gunther;Clarke, Alan R;Mueller, Ulrich;Hynes, Nancy E;Streuli, Charles H
通讯作者：
Streuli, Charles H
影响因子：
3.3
作者：
Faraldo, MM;Deugnier, MA;Glukhova, MA
通讯作者：
Glukhova, MA