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Giancotti/Elsevier; C! j* x, p- x0 i: p
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When endothelial cells adhere to the extracellular matrix protein fibronectin, they can proliferate in response to growth factors. Adhesion to laminin, however, brings their cell cycles to a dead stop. Why? Given that the response depends on the composition of the extracellular matrix, Filippo Giancotti and his colleagues at the Memorial Sloan-Kettering Cancer Center (New York, NY) proposed in 1996 that progression through the cell cycle depends on signaling from a cell's particular repertoire of adhesion receptors called integrins.; F1 V7 E5 a' _) d& k; g
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Integrins do not act alone, however. "Our major hypothesis in the past few years has been that the integrins that are able to promote proliferation do so by cooperating with growth factor receptors," says Giancotti. That control was thought to be exerted via the MAP kinase ERK, at the level of cyclin D1 transcription. The new paper, however, reports that ERK activation occurs when cells are plated on either fibronectin or laminin, whereas it is Rac activation that is specific to the proliferation- permissive fibronectin. Furthermore, activated Rac promotes translation, not transcription, of Cyclin D1, initiating progression through G1 to the S phase of the cell cycle.
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The specific signaling functions of integrins that promote either proliferation or growth arrest are important in many cell types. "The general issue is the cell's ability to interpret positional information," says Giancotti. In angiogenesis, for example, fibronectin may promote endothelial cell proliferation during the invasive phase, then laminin may aid differentiation by inducing cell cycle exit.
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( t# p; m! v# B, TMettouchi, A., et al. 2001. Mol. Cell. 8:115–127.(Signaling from focal adhesions gets cell) |
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发表于 2009-3-5 23:40
发表于 2015-6-6 13:40
