Map kinase signaling path

Multi-stage signal transduction pathways of MAP kinases (mitogen-activated protein kinases). These are involved in the regulation of embryogenesis, cell differentiation, cell growth and apoptosis.

The signaling pathways include at least 3 "in series" connected kinases (see below Raf kinases). The MAPK signaling cascade(RAS→ BRAF → → MEK→ ERK→cell proliferation / cell differentiation), which runs intracellularly and is connected in series, is a fundamental cell biological process through which the vital cell functions "proliferation and differentiation" are decisively regulated. The receptor kinases are also phosphorylated in this order and thus activated (phosphorylation cascades). They are used to transmit signals from the cell membrane into the cell nucleus and interlock like gears.

• MAP kinase kinase kinase (MAP-3K, also: MAP-KKK)
• MAP kinase kinase (MAP-2K, also MAP-KK)
• MAP Kinase (MAP-K)

The signal transduction is triggered by 3 different stimuli (but one of the MAP kinases is always active):

• Activation via mitogens (ERK1/ERK2 cascade); activation of this signaling pathway leads to cell growth, proliferation and differentiation. This signalling pathway is hyperactivated in 30% of all cancers (see photocarcinogenesis, see MYC gene below).
• Activation via cytokines (e.g. tumour necrosis factors or interleukins) activates the cascade MLKs/TAK/ASK1 → MKK 3/6 → p38/MAPK-α/β. The activation of this signalling cascade leads to inflammatory reactions, apoptosis, growth or differentiation.
• Activation via stress, UV radiation, heat shock or osmosis. Activation is the cascade MLKs/ASK-1/MEKK-1/4 → MKK-4/7 → SAPK/JNK-1/2/3. This causes responses such as inflammation, apoptosis, growth or differentiation.

After ligand binding, the receptors dimerize and are activated by autophosporylation of their tyrosine residues at the intracellular receptor domain. These phosphorylated tyrosine residues act as binding sites for the adapter proteins, which then activate further signalling molecules by phosphorylation.