期刊
MOLECULAR BIOLOGY OF THE CELL
卷 19, 期 5, 页码 2135-2146出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E07-10-0991
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资金
- Cell Dynamics Research Center [R11-2007-007-02001-0]
- Bioimaging Research Center
- Ministry of Science and Technology, South Korea [2006-02594]
- U. S. National Institutes of Health [GM049882]
- National Research Foundation of Korea [R11-2007-007-02001-0, 2006-02594] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Reciprocal cooperative signaling by integrins and growth factor receptors at G1 phase during cell cycle progression is well documented. By contrast, little is known about the cross-talk between integrin and transforming growth factor (TGF)-beta signaling. Here, we show that integrin signaling counteracts the inhibitory effects of TGF-beta on cell growth and that this effect is mediated by p130Cas (Crk-associated substrate, 130 kDa). Adhesion to fibronectin or laminin reduces TGF-beta induced Smad3 phosphorylation and thus inhibits TGF-beta-mediated growth arrest; loss of p130Cas abrogates these effects. Loss and gain of function studies demonstrated that, once tyrosine-phosphorylated via integrin signaling, p130Cas binds to Smad3 and reduces phosphorylation of Smad3. That in turn leads to inhibition of p15 and p21 expression and facilitation of cell cycle progression. Thus, p130Cas-mediated control of TGF-beta/Smad signaling may provide an additional clue to the mechanism underlying resistance to TGF-beta-induced growth inhibition.
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