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Maybe there can be too much of a good thing. A new report from Woodring et al. (page 879) provides the basis for a self-limiting interaction between F-actin and c-Abl. Although the authors find that c-Abl is an important activator of actin polymerization, the resultant F-actin can shut down c-Abl, thus completing a feedback loop that limits actin polymerization.The rapid assembly and disassembly of actin fibers is required for controlling cell migration, changing cell morphology, and extending the dendrites and axons of neurons. Some extracellular signals that cause alterations in the F-actin cytoskeleton, such as integrin clustering, have also been shown to activate c-Abl, a nonreceptor tyrosine kinase with an F-actin binding site. In vitro, binding to F-actin inhibits the kinase activity of c-Abl.7 j7 Z% r1 v) ^8 s! v* H
7 i- ]2 q: R$ t0 s; eWoodring et al. now demonstrate that c-Abl promotes actin polymerization. c-Abl stimulates the formation of F-actin microspikes in both spreading fibroblasts and neurites of embryonic cortical neurons. Whereas inhibition of c-Abl kinase activity blocked the formation of F-actin microspikes, expression of an activated form led to more microspikes, independent of cell surface signals. The stimulation occurred even under conditions in which Rho-family GTPases were inhibited, indicating that either c-Abl acts downstream of Rho or a GTPase-independent actin polymerization pathway exists. Downstream, c-Abl previously has been shown to associate with WAVE1, an activator of the Arp2/3 complex, which is known to initiate actin polymerization.# x p7 G% F/ l# z. ?& r# Z. A b
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The inhibition of c-Abl could provide a reciprocal regulation to limit the lifespan of F-actin protrusions. The inhibitory effect of actin on c-Abl may be suppressed in attached cells through the binding of another molecule to c-Abl or the redistribution of c-Abl and F-actin upon attachment, thus promoting actin-dependent spreading of the attached cell.(c-Abl (red) that cannot bind actin (righ) |
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发表于 2009-3-6 00:15
发表于 2015-5-25 17:18
