Downstream targets of ERKs include transcription factors and immediate early genes that play roles in mediating drug-induced synaptic plasticity, including ribosomal S6 kinase (RSK) and mitogen- and stress-stimulated kinase 1 (MSK1). These downstream kinases phosphorylate and activate the cAMP response element binding protein (CREB). ERKs also can directly phosphorylate the Elk-1 transcription factor. Activation of CREB and Elk-1 can lead to the transcription of the immediate early genes c-fos and zif268, which are induced by several drugs of abuse.2
