Transcription Factor Regulation (CREB, Elk-1 and c-Fos) The transcription factor CREB binds to the cAMP response element (CRE) and activates gene transcription in response to a wide variety of extracellular signals (including growth factors, hormones, and neurotransmitters). Transcriptional activation of CREB is controlled through phosphorylation at Ser133 by p90Rsk and the p44/42 MAP kinase. The transcriptional activity of the proto-oncogene c-Fos has been implicated in cell growth, differentiation, and development. Fos is induced by many stimuli, ranging from mitogens to pharmacological agents. c-Fos has been shown to be associated with another proto-oncogene, c-Jun, and together they bind to the AP-1 binding site to regulate gene transcription. Like CREB, c-Fos is regulated by p90Rsk. Elk-1 is a transcription factor that is activated by the MAP kinase-mediated phosphorylation at a Ser/Thr cluster at the C-terminus. Activated Elk-1 binds to the serum response element (SRE) to induce gene transcription in response to serum and growth factors. Recent studies have also demonstrated that Elk-1 is a target for the stress-activated kinase SAPK/JNK. References: Herdegen, T., and Leah, J.D., Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins. Brain Res. Brain Res. Rev. 28, 370-490 (1998). Davis, R.J., Transcriptional regulation by MAP kinases. Mol. Reprod. Dev. 42, 459-467 (1995).