How does MAPK cascade alter the transcriptional activity of a cell?

MAPK's are mitogen-activated protein kinases. (Mitogens are extracellular signals that induce mitosis and cell division). MAPK cascades mediate hormone signals via pathways that result in phosphorylation of target enzymes by protein kinases. The target of phosphorylation is often another protein kinase, which then phosphorylates a third protein kinase and so on MAPK cascades mediate signaling initiated by a variety of growth factors, such as platelet derived growth factors (PDGF) and epidermal growth factor (EGF). The three families are:  1) MAPK (ERK)  2)MAPKKs (MEK)  3) MAPKKK (Elk).

Regulation of gene expression by insulin through a MAP kinase cascade:

• INSR is auto phosphorylated (INSR-Insulin receptor) which opens up the active site such that enzyme receptor (tyrosine kinase) can phosphorylate other proteins.
• After auto phosphorylation, it binds to its target Insulin Receptor Substrate 1 (IRS-1).
•  A P-Tyr residue (i.e., phosphorylated tyrosine residue) binds to the SH2 domain of the protein Grb 2. (Grb 2 is an adaptor protein; its function is to bring together IRS-1 and the protein Sos). Grb 2 has two domains : an SH2 domain that binds its P-Tyr to IRS 1 and a second SH3 domain that binds to proline rich region of Sos.
• When bound to Grb 2, Sos acts as a guanosine nucleotide- exchange factor (GEF), catalyzing the replacement of bound GDP with GTP on Ras, a G protein. Ras can exist in either the GTP-bound (active) or GDP-bound (inactive) conformation. When GTP binds, Ras can activate a protein kinases- Raf 1, MEK and ERK.
• Raf 1, MEK and ERK form a cascade in which each kinase activates the next by phosphorylation.
• When activated, ERK enters the nucleus and phosphorylates transcription factors like Elk 1.
• Phosphorylated Elk1 joins SRF to stimulate the transcription of genes needed for cell division.