positive regulation of ERK1 and ERK2 cascade

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade. [GOC:mah]

Positive regulation of the ERK1 and ERK2 cascade, also known as the Ras-Raf-MEK-ERK pathway, is a fundamental signaling pathway in eukaryotic cells that plays a critical role in a diverse array of cellular processes including cell growth, proliferation, differentiation, survival, and apoptosis. This cascade is initiated by extracellular stimuli such as growth factors, hormones, and cytokines, which bind to cell surface receptors and trigger a chain of events leading to the activation of ERK1 and ERK2. The pathway involves multiple steps:

1. Receptor Activation and Ligand Binding: Extracellular stimuli bind to specific transmembrane receptors, such as receptor tyrosine kinases (RTKs), triggering their dimerization and autophosphorylation.

2. Ras Activation: Activated receptors recruit adaptor proteins and activate Ras, a small GTPase. Ras binds GTP and becomes active, initiating the downstream signaling cascade.

3. Raf Activation: Activated Ras interacts with and activates Raf, a serine/threonine protein kinase. Raf phosphorylation and activation occur in a complex process involving multiple interactions with other proteins, including MEK, and scaffolding proteins.

4. MEK Activation: Activated Raf phosphorylates and activates MEK (MAPK/ERK kinase), another dual-specificity kinase. MEK specifically phosphorylates ERK1 and ERK2 on specific threonine and tyrosine residues.

5. ERK1 and ERK2 Activation: MEK activates ERK1 and ERK2 by dual phosphorylation, leading to their conformational change and activation. Activated ERK1 and ERK2 translocate to the nucleus and cytoplasm, triggering a wide range of downstream signaling events.

6. Transcriptional Regulation: In the nucleus, activated ERK1 and ERK2 phosphorylate transcription factors, such as Elk-1, c-Fos, and c-Jun, promoting their activation and altering gene expression. This regulation influences the expression of genes involved in cell growth, proliferation, differentiation, and other cellular processes.

7. Cytoplasmic Signaling: ERK1 and ERK2 also regulate cytoplasmic signaling pathways by phosphorylating and activating various proteins involved in cell survival, apoptosis, and cytoskeletal dynamics.

The positive regulation of the ERK1 and ERK2 cascade is tightly controlled by a complex interplay of various regulatory mechanisms, including feedback loops, scaffolding proteins, and protein phosphatases. This ensures that the pathway is activated only when needed and that its activity is properly regulated. Dysregulation of the ERK1 and ERK2 cascade is associated with various human diseases, including cancer, neurodegenerative disorders, and cardiovascular diseases. Understanding the intricacies of this pathway is crucial for developing novel therapeutic strategies targeting these diseases.'
"

Proteins (97)

Compounds (2,525)