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

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.

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Wozniak MA, Cheng CQ, Shen CJ, Gao L, Olarerin-George AO, Won KJ, Hogenesch JB, Chen CS