The immediately-early genes fos and jun activation by map kinase-mediated signaling
The immediate early genes are a class of genes which involved in many important cellular processes. The expression of immediate early genes is rapid and transient. They are commonly induced to express following a variety extracellular signal. There are several groups of these extracellular stimuli: depolarization, neurotransmitters, growth factors, cellular stress, and elevation of intracellular calcium concentration. These extracellular challenges promote activation of a range of interdependent signaling pathways within the cell. That process eventually leads to induction of immediate early genes expression. Several signal transduction pathways take part in immediate early genes activation. Possibly the most important among these transduction systems is MAPK (mitogen-activated protein kinase) signaling pathway. The activation of MAPK cascades includes several steps. At first activation of small GTP-binding proteins (Ras, Rac, Cdc42) results in transmission the signal to the MAPK kinase kinase (MAP3K). Subsequently, the signal is transmitted down the cascade by enzymes located at the following steps, which are referred to as MAPK kinase (MAPKK), MAPK, and MAPK-activated protein kinase (MAPKAPK). MAPK signaling pathway includes at least four cascades that are named according to the subgroup of their MAPK components: extracellular signal-regulated kinase (ERK), p38MAPK, c-Jun N-terminal kinase (JNK) and Big MAPK (BMK). Each one plays an important role in the immediate early genes activation. The signal transduction eventually leads to the phosphorylation and activation of regulatory proteins involved in the immediate early gene expression, including transcription factors such as ELK1, АР- 1, NF-kB, CREB, and MEF2C. Also signal transduction results in histone H3 modifications. All these changes play a crucial role in the immediate early genes activation.