MAPK cascade

Definition

Target type: biologicalprocess

An intracellular protein kinase cascade containing at least a MAP kinase (MAPK). It starts with the activation of a MAP3K, and the consecutive activation of a MPK2K and a MAPK. The cascade can also contain an additional tier: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinase in the downstream tier to transmit a signal within a cell. [PMID:20811974, PMID:9561267]

The mitogen-activated protein kinase (MAPK) cascade is a highly conserved signaling pathway that plays a critical role in cellular responses to a wide range of stimuli, including growth factors, stress, and inflammation. The pathway consists of a three-tiered kinase module, where each kinase phosphorylates and activates the next kinase in the cascade. This phosphorylation cascade ultimately leads to the activation of transcription factors, which regulate gene expression and cellular responses.

The MAPK cascade is initiated by the binding of an extracellular signal to a receptor on the cell surface. This binding event activates a series of intracellular signaling molecules, ultimately leading to the activation of a MAPK kinase kinase (MAPKKK), the first kinase in the cascade. MAPKKKs activate MAPK kinases (MAPKKs), which in turn activate MAPKs.

The MAPK cascade is highly regulated, with multiple feedback loops and crosstalk with other signaling pathways. This ensures that the pathway is activated only when appropriate and that the cellular response is tightly controlled.

The MAPK cascade is involved in a wide range of cellular processes, including cell proliferation, differentiation, survival, and apoptosis. Dysregulation of the MAPK cascade is implicated in various diseases, including cancer, inflammation, and neurodegenerative disorders.

Here is a detailed description of the MAPK cascade:

1. **Initiation:** The MAPK cascade is initiated by the activation of a receptor tyrosine kinase (RTK). RTKs are transmembrane proteins that bind extracellular ligands, such as growth factors. Ligand binding triggers the autophosphorylation of the RTK, which in turn activates downstream signaling molecules, including the adapter protein Grb2 and the guanine nucleotide exchange factor SOS. SOS activates Ras, a small GTPase that plays a critical role in the MAPK cascade.

2. **Activation of the MAPK cascade:** Active Ras recruits and activates the MAPKKK Raf. Raf phosphorylates and activates MEK, a MAPKK. MEK then phosphorylates and activates ERK, a MAPK.

3. **Signal transduction:** Activated ERK translocates to the nucleus, where it phosphorylates and activates transcription factors, such as Elk-1 and c-Fos. These transcription factors regulate the expression of genes involved in cell proliferation, differentiation, and survival.

4. **Termination:** The MAPK cascade is terminated by the inactivation of Ras, the dephosphorylation of Raf, MEK, and ERK, and the degradation of activated transcription factors.

5. **Regulation:** The MAPK cascade is tightly regulated by a complex network of feedback loops and crosstalk with other signaling pathways. This ensures that the pathway is activated only when appropriate and that the cellular response is tightly controlled.

The MAPK cascade is a complex and highly regulated pathway that plays a critical role in cellular responses to a wide range of stimuli. Dysregulation of the MAPK cascade is implicated in various diseases, including cancer, inflammation, and neurodegenerative disorders.'
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Proteins (80)

Compounds (1,064)