How can signals transmitted by second messengers influence gene expression?

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Second messengers convey information from receptors to the nucleus so gene expression can change. When a signal increases levels of messengers like cAMP or Ca2+, they activate kinases or phosphatases that either move into the nucleus or activate transcription factors that do. A classic example is cAMP activating PKA, which phosphorylates CREB; phosphorylated CREB binds DNA at CRE sites and recruits coactivators to drive transcription of target genes. Calcium, via calmodulin, activates CaMKs or other factors that modify transcription factors or chromatin, leading to new patterns of gene expression. Through these pathways, the external signal is transformed into changes in mRNA production and, consequently, protein synthesis and cell behavior. Signals that stay confined to the cytosol or are exported out of the cell, or that are degraded, won’t drive these transcriptional changes, because the nucleus is where gene expression is controlled and needs the activated transcription factors to reach it.