Abstract:
:We recently reported that Rho kinase is required for sustained ERK signaling and the consequent mid-G(1) phase induction of cyclin D1 in fibroblasts. The results presented here indicate that these Rho kinase effects are mediated by the formation of stress fibers and the consequent clustering of alpha5beta1 integrin. Mechanistically, alpha5beta1 signaling and stress fiber formation allowed for the sustained activation of MEK, and this effect was mediated upstream of Ras-GTP loading. Interestingly, disruption of stress fibers with ML-7 led to G(1) phase arrest while comparable disruption of stress fibers with Y27632 (an inhibitor of Rho kinase) or dominant-negative Rho kinase led to a more rapid progression through G(1) phase. Inhibition of either MLCK or Rho kinase blocked sustained ERK signaling, but only Rho kinase inhibition allowed for the induction of cyclin D1 and activation of cdk4 via Rac/Cdc42. The levels of cyclin E, cdk2, and their major inhibitors, p21(cip1) and p27(kip1), were not affected by inhibition of MLCK or Rho kinase. Overall, our results indicate that Rho kinase-dependent stress fiber formation is required for sustained activation of the MEK/ERK pathway and the mid-G(1) phase induction of cyclin D1, but not for other aspects of cdk4 or cdk2 activation. They also emphasize that G(1) phase cell cycle progression in fibroblasts does not require stress fibers if Rac/Cdc42 signaling is allowed to induce cyclin D1.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Roovers K,Assoian RKdoi
10.1128/mcb.23.12.4283-4294.2003subject
Has Abstractpub_date
2003-06-01 00:00:00pages
4283-94issue
12eissn
0270-7306issn
1098-5549journal_volume
23pub_type
杂志文章,收录出版abstract::To distinguish among possible mechanisms of repair of a double-strand break (DSB) by gene conversion in budding yeast, Saccharomyces cerevisiae, we employed isotope density transfer to analyze budding yeast mating type (MAT) gene switching in G2/M-arrested cells. Both of the newly synthesized DNA strands created durin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01654-06
更新日期:2006-12-01 00:00:00
abstract::The eukaryotic genome is divided into chromosomal domains of distinct gene activities. Transcriptionally silent chromatin tends to encroach upon active chromatin. Barrier elements that can block the spread of silent chromatin have been documented, but the mechanisms of their function are not resolved. We show that the...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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doi:10.1128/mcb.4.3.507
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.3.1194
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.10.3388
更新日期:1986-10-01 00:00:00
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pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.6.2591
更新日期:1990-06-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00211-08
更新日期:2008-11-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.19.8487-8503.2004
更新日期:2004-10-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.7.2923-2931.2004
更新日期:2004-04-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.7.2997
更新日期:1992-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/mcb.5.6.1534
更新日期:1985-06-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.2.672
更新日期:1987-02-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.5.2214
更新日期:1988-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/mcb.23.6.2202-2212.2003
更新日期:2003-03-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:1994-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:2013-11-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.11.6041
更新日期:1990-11-01 00:00:00
abstract::Y-27632, an inhibitor of the Rho-associated kinase ROCK, is a therapeutic lead for Huntington disease (HD). The downstream targets that mediate its inhibitory effects on huntingtin (Htt) aggregation and toxicity are unknown. We have identified profilin, a small actin-binding factor that also interacts with Htt, as bei...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2008-09-01 00:00:00
abstract::The human splicing factor 2, also called human alternative splicing factor (hASF), is the prototype of the highly conserved SR protein family involved in constitutive and regulated splicing of metazoan mRNA precursors. Here we report that the Drosophila homologue of hASF (dASF) lacks eight repeating arginine-serine di...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.4.1345-1359.2001
更新日期:2001-02-01 00:00:00
abstract::Mouse neuroblastoma Neuro-2A cells produce transforming growth factors during exponential growth in a defined hormone-free medium, which, on Bio-Gel columns in 1 M HAc, elute at a molecular size of 15 to 20 kilodaltons (kDa). These neuroblastoma-derived transforming growth factors have strong mitogenic activity, but t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.9.2289
更新日期:1985-09-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2010-01-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.4.2096
更新日期:1991-04-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.6.2748
更新日期:1989-06-01 00:00:00
abstract::The Epstein-Barr virus BRLF1 and BZLF1 genes are the first viral genes transcribed upon induction of the viral lytic cycle. The protein products of both genes (referred to here as Rta and Zta, respectively) activate expression of other viral genes, thereby initiating the lytic cascade. Among the viral antigens express...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.5.3041
更新日期:1994-05-01 00:00:00