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, among other things.
Map kinase signaling path
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The signaling pathways comprise at least three kinases switched "in series" (see below Raf kinases). The MAPK signaling cascade(RAS→ BRAF → MEK→ ERK→cell proliferation / cell differentiation), which takes place intracellularly and is connected in series, is a fundamental cell biological process that decisively regulates the vital cell functions "proliferation and differentiation". The receptor kinases are also phosphorylated in this sequence and thus activated (phosphorylation cascades). They serve to transmit signals from the cell membrane to the cell nucleus and interlock like cogwheels.
- 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 (whereby one of the MAP kinases is always activated):
- Activation via mitogens (ERK1/ERK2 cascade); activation of this signaling pathway leads to cell growth, proliferation and differentiation. This signaling pathway is hyperactivated in 30 % of all cancers (see below photocarcinogenesis, see below MYC gene).
- Activation via cytokines (e.g. tumor necrosis factors or interleukins); activates the MLKs/TAK/ASK1 → MKK 3/6 → p38/MAPK-α/β cascade. Activation of this signaling cascade leads to inflammatory reactions, apoptosis, growth or differentiation.
- Activation via stress, UV radiation, heat shock or osmosis. The MLKs/ASK-1/MEKK-1/4 → MKK-4/7 → SAPK/JNK-1/2/3 cascade is activated, causing responses such as inflammation, apoptosis, growth or differentiation.
After ligand binding, the receptors dimerize and are activated by autophosphorylation 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 signaling molecules by phosphorylation.