Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Expression data from serum-stimulated NIH 3T3 cells stably expressing control (pLKO.1) vector or shRNAs targeting Net or Sap-1


ABSTRACT: Although much is known about focal adhesion signaling induced by cell adhesion, how adhesion directs changes in transcription to control cell behavior is far less understood. Here we describe a novel mechanism by which changes in adhesion switch the activities of the mitogen-activated protein kinases (MAPKs) c-Jun N-terminal kinase (JNK) and p38, resulting in the differential activation and promoter occupancy of the SRF cofactors, the ternary complex factors (TCFs) Sap-1 and Net. Adhesion-induced MAPK/TCF switching controls immediate early gene expression and proliferation. This mechanism is of physiological relevance, as proliferative regulation by the TCFs is conserved in an ex ovo model of angiogenesis. Furthermore, microarray analysis identified novel genes and adhesive functions regulated by Sap-1 and Net. Thus our data identify the TCFs as key regulators of adhesion-induced transcription and cell behavior. [mRNA profiling]: NIH 3T3 cells were plated on fibronectin-coated plastic for two hours, then rinsed with PBS and serum-starved overnight. 20% bovine serum was then added to the cells for one hour. Cells from three biological replicates were lysed and RNA extracted with a Qiagen RNeasy mini kit and prepared for hybridization on Affymetrix GeneChip Mouse Gene 1.0 ST microarrays.

ORGANISM(S): Mus musculus

SUBMITTER: Michele Wozniak 

PROVIDER: E-GEOD-26640 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Adhesion regulates MAP kinase/ternary complex factor exchange to control a proliferative transcriptional switch.

Wozniak Michele A MA   Cheng Catherine Q CQ   Shen Colette J CJ   Gao Lin L   Olarerin-George Anthony O AO   Won Kyoung-Jae KJ   Hogenesch John B JB   Chen Christopher S CS  

Current biology : CB 20121011 21


<h4>Background</h4>The ternary complex factors (TCFs; Elk1, Net, and Sap-1) are growth factor-responsive transcription cofactors of serum response factor (SRF) and are activated by MAP kinase (MAPK) phosphorylation to regulate immediate early gene transcription. Although cell adhesion also can regulate immediate early genes and proliferation, the mechanism for this effect has remained unexplored.<h4>Results</h4>Restricting adhesion and spreading of G(0)-synchronized cells on substrates with decr  ...[more]

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