The roles of integrin-linked kinase in the regulation of myogenic differentiation.
The roles of integrin-linked kinase in the regulation of myogenic differentiation.
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DOI：
10.1083/jcb.150.4.861
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发表时间：
2000-08-21
期刊：
影响因子：
--
通讯作者：
Wu C
中科院分区：
文献类型：
--
作者：
Huang Y;Li J;Zhang Y;Wu C
成肌分化是一个高度协调的多步骤过程，受生长因子和细胞粘附的协调调节。我们在这里表明，整合素连接激酶（ILK），细胞内的整合素和PINCH结合丝氨酸/苏氨酸蛋白激酶，是一个重要的调节肌分化。ILK在诱导终末肌源性分化之前和之后都在C2 C12成肌细胞中大量表达。然而，在Triton X-100可溶性细胞组分中显著量的ILK在终末肌源性分化期间显著减少，表明ILK参与肌源性分化的细胞控制。为了进一步研究这一点，我们在C2 C12成肌细胞中过表达ILK的野生型和突变型。ILK在成肌细胞中的过表达抑制了成肌蛋白（肌细胞生成素、MyoD和肌球蛋白重链）的表达以及随后的多核肌管的形成。此外，消除ILK的PINCH结合或激酶活性的突变消除了其抑制肌源性蛋白表达的能力，并允许肌管形成。尽管ILK突变体的过表达允许终末肌源性分化的起始，但源自过表达ILK突变体的成肌细胞的肌管经常表现出异常形态（含有成簇核的巨大肌管），表明ILK不仅在初始决策过程中起作用，而且在肌源性分化的后期阶段（融合或维持肌管完整性）也起作用。此外，我们表明，ILK的过度表达，但不是PINCH结合缺陷或激酶缺陷的ILK突变体，防止MAP激酶的失活，这是强制性的肌源性分化的启动。最后，抑制MAP激酶激活逆转了ILK诱导的成肌蛋白表达抑制。因此，ILK可能通过调节MAP激酶的活化来影响肌源性分化的初始决策过程。
Myogenic differentiation is a highly orchestrated, multistep process that is coordinately regulated by growth factors and cell adhesion. We show here that integrin-linked kinase (ILK), an intracellular integrin– and PINCH-binding serine/threonine protein kinase, is an important regulator of myogenic differentiation. ILK is abundantly expressed in C2C12 myoblasts, both before and after induction of terminal myogenic differentiation. However, a noticeable amount of ILK in the Triton X-100–soluble cellular fractions is significantly reduced during terminal myogenic differentiation, suggesting that ILK is involved in cellular control of myogenic differentiation. To further investigate this, we have overexpressed the wild-type and mutant forms of ILK in C2C12 myoblasts. Overexpression of ILK in the myoblasts inhibited the expression of myogenic proteins (myogenin, MyoD, and myosin heavy chain) and the subsequent formation of multinucleated myotubes. Furthermore, mutations that eliminate either the PINCH-binding or the kinase activity of ILK abolished its ability to inhibit myogenic protein expression and allowed myotube formation. Although overexpression of the ILK mutants is permissive for the initiation of terminal myogenic differentiation, the myotubes derived from myoblasts overexpressing the ILK mutants frequently exhibited an abnormal morphology (giant myotubes containing clustered nuclei), suggesting that ILK functions not only in the initial decision making process, but also in later stages (fusion or maintaining myotube integrity) of myogenic differentiation. Additionally, we show that overexpression of ILK, but not that of the PINCH-binding defective or the kinase-deficient ILK mutants, prevents inactivation of MAP kinase, which is obligatory for the initiation of myogenic differentiation. Finally, inhibition of MAP kinase activation reversed the ILK-induced suppression of myogenic protein expression. Thus, ILK likely influences the initial decision making process of myogenic differentiation by regulation of MAP kinase activation.
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DOI：
10.1016/s1044-5781(06)80020-4
发表时间：
1995-01-01
期刊：
Seminars in Developmental Biology
影响因子：
--
作者：
McDonald, Kevin A.;Horwitz, Alan F.;Knudsen, Karen A.
通讯作者：
Knudsen, Karen A.
DOI：
10.1083/jcb.147.7.1391
发表时间：
1999-12-27
期刊：
The Journal of cell biology
影响因子：
--
作者：
Li J;Mayne R;Wu C
通讯作者：
Wu C
影响因子：
2.7
作者：
BOETTIGER, D;ENOMOTOIWAMOTO, M;CHIQUETEHRISMANN, R
通讯作者：
CHIQUETEHRISMANN, R
影响因子：
7.5
作者：
Durbeej, M;Henry, MD;Campbell, KP
通讯作者：
Campbell, KP
影响因子：
64.5
作者：
MENKO, AS;BOETTIGER, D
通讯作者：
BOETTIGER, D