Response to the Signal

Gene Expression

Some signal transduction pathways regulate the transcription of RNA. Others regulate the translation of proteins from mRNA. An example of a protein that regulates translation in the nucleus is the MAP kinase ERK. The MAPK/ERK pathway (also known as the Ras-Raf-MEK-ERK pathway) is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the nuclear DNA. ERK is activated in a phosphorylation cascade when epidermal growth factor (EGF) binds the EGF receptor (see ). Upon phosphorylation, ERK enters the nucleus and activates a protein kinase that, in turn, regulates protein translation (Figure).

This illustration shows the pathway by which ERK, a MAP kinase, activates protein synthesis. Phosphorylated ERK phosphorylates MNK1, which in turn phosphorylates eIF-4E, which is associated with mRNA. When eIF-4E is phosphorylated, the mRNA unfolds and protein synthesis begins.
ERK is a MAP kinase that activates translation when it is phosphorylated. ERK phosphorylates MNK1, which in turn phosphorylates eIF-4E, an elongation initiation factor that, with other initiation factors, is associated with mRNA. When eIF-4E becomes phosphorylated, the mRNA unfolds, allowing protein synthesis in the nucleus to begin. (See for the phosphorylation pathway that activates ERK.)

Another mechanism of gene regulation involves PKC, which can interact with is a protein that acts as an inhibitor. An inhibitor is a molecule that binds to a protein and prevents it from functioning or reduces its function. In this case, the inhibitor is a protein called Iκ-B, which binds to the regulatory protein NF-κB. (The symbol κ represents the Greek letter kappa.) When Iκ-B is bound to NF-κB, the complex cannot enter the nucleus of the cell, but when Iκ-B is phosphorylated by PKC, it can no longer bind NF-κB, and NF-κB (a transcription factor) can enter the nucleus and initiate RNA transcription. In this case, the effect of phosphorylation is to inactivate an inhibitor and thereby activate the process of transcription.

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