Quantitative changes in integrin and focal adhesion signaling regulate myoblast cell cycle withdrawal.
Quantitative changes in integrin and focal adhesion signaling regulate myoblast cell cycle withdrawal.
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DOI：
10.1083/jcb.144.6.1295
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发表时间：
1999-03-22
期刊：
影响因子：
--
通讯作者：
Horwitz AF
中科院分区：
文献类型：
--
作者：
Sastry SK;Lakonishok M;Wu S;Truong TQ;Huttenlocher A;Turner CE;Horwitz AF
我们之前证明了整合素α亚基及其胞浆结构域在控制细胞周期退出和终末分化开始方面的相反作用（Sastry，S.，M. Lakonishok，D.托马斯，J. Muschler和A.F.霍维茨1996. 133：169-184）。整合素α5或α6A亚基在原代鹌鹑成肌细胞中的异位表达分别降低或增强细胞周期退出的可能性。在这项研究中，我们解决了整合素α亚基比例的变化调节这一决定的机制。截短的α5或α6A的异位表达表明α5胞质结构域允许增殖途径，而α6A胞质结构域的COOH末端11个氨基酸抑制增殖并促进分化。α5和α6A胞质结构域似乎不直接启动这些信号，而是调节β1信号。异位表达的IL 2 R-α5或IL 2 R-α6A对成肌细胞表型没有可检测的影响。然而，β1A整联蛋白亚基或IL 2 R-β1A的异位表达自主地抑制分化并维持增殖状态。扰动α5或α6A比率也显著影响β1整联蛋白信号通路的活化。异位α5表达增强桩蛋白和丝裂原活化蛋白（MAP）激酶的表达和活化，而对粘着斑激酶（FAK）几乎没有影响。相反，异位α6A表达抑制FAK和MAP激酶活化，对桩蛋白的影响较小。FAK、桩蛋白和MAP/erk激酶（MEK）的野生型和突变形式的异位表达证实了这些相关性。这些数据表明（a）增殖信号传导（即，（B）干扰α亚基比例改变桩蛋白表达和磷酸化以及FAK和MAP激酶活化;（c）通过整联蛋白和粘着斑组分的粘着信号传导水平的定量变化调节成肌细胞退出细胞周期的决定，部分通过MAP激酶。
We previously demonstrated contrasting roles for integrin α subunits and their cytoplasmic domains in controlling cell cycle withdrawal and the onset of terminal differentiation (Sastry, S., M. Lakonishok, D. Thomas, J. Muschler, and A.F. Horwitz. 1996. J. Cell Biol. 133:169–184). Ectopic expression of the integrin α5 or α6A subunit in primary quail myoblasts either decreases or enhances the probability of cell cycle withdrawal, respectively. In this study, we addressed the mechanisms by which changes in integrin α subunit ratios regulate this decision. Ectopic expression of truncated α5 or α6A indicate that the α5 cytoplasmic domain is permissive for the proliferative pathway whereas the COOH-terminal 11 amino acids of α6A cytoplasmic domain inhibit proliferation and promote differentiation. The α5 and α6A cytoplasmic domains do not appear to initiate these signals directly, but instead regulate β1 signaling. Ectopically expressed IL2R-α5 or IL2R-α6A have no detectable effect on the myoblast phenotype. However, ectopic expression of the β1A integrin subunit or IL2R-β1A, autonomously inhibits differentiation and maintains a proliferative state. Perturbing α5 or α6A ratios also significantly affects activation of β1 integrin signaling pathways. Ectopic α5 expression enhances expression and activation of paxillin as well as mitogen-activated protein (MAP) kinase with little effect on focal adhesion kinase (FAK). In contrast, ectopic α6A expression suppresses FAK and MAP kinase activation with a lesser effect on paxillin. Ectopic expression of wild-type and mutant forms of FAK, paxillin, and MAP/erk kinase (MEK) confirm these correlations. These data demonstrate that (a) proliferative signaling (i.e., inhibition of cell cycle withdrawal and the onset of terminal differentiation) occurs through the β1A subunit and is modulated by the α subunit cytoplasmic domains; (b) perturbing α subunit ratios alters paxillin expression and phosphorylation and FAK and MAP kinase activation; (c) quantitative changes in the level of adhesive signaling through integrins and focal adhesion components regulate the decision of myoblasts to withdraw from the cell cycle, in part via MAP kinase.
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影响因子：
7.8
作者：
Belkin, AM;Zhidkova, NI;Balzac, F;Altruda, F;Tomatis, D;Maier, A;Tarone, G;Koteliansky, VE;Burridge, K
通讯作者：
Burridge, K
影响因子：
2.7
作者：
BOETTIGER, D;ENOMOTOIWAMOTO, M;CHIQUETEHRISMANN, R
通讯作者：
CHIQUETEHRISMANN, R
影响因子：
2.7
作者：
BLASCHUK, KL;HOLLAND, PC
通讯作者：
HOLLAND, PC
DOI：
10.1083/jcb.135.4.1109
发表时间：
1996-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Brown MC;Perrotta JA;Turner CE
通讯作者：
Turner CE
DOI：
10.1083/jcb.113.2.405
发表时间：
1991-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
de Curtis I;Quaranta V;Tamura RN;Reichardt LF
通讯作者：
Reichardt LF