MitogenActivated

Mitogen-activated describes cellular signaling events triggered by mitogens, extracellular cues such as growth factors, hormones, or cytokines that stimulate cell proliferation and division. The term is often used in reference to mitogen-activated protein kinases (MAPKs), a family of serine/threonine kinases central to transducing mitogenic signals.

A canonical example is the mitogen-activated protein kinase cascade, a three-tiered relay that channels signals from cell-surface receptors to the nucleus. In this pathway, a mitogenic signal activates a MAP kinase kinase kinase (MAPKKK, such as RAF), which phosphorylates a MAP kinase kinase (MAPKK, such as MEK), which in turn activates a MAP kinase (MAPK, such as ERK1/2). Activated MAPKs phosphorylate a range of substrates, including transcription factors like ELK1 and components of the transcriptional machinery, leading to changes in gene expression that promote cell-cycle progression and proliferation.

MAPKs are organized into subfamilies, including ERK1/2, JNK, and p38, each responding to distinct types of stimuli. ERK1/2 commonly respond to growth factors and mitogens, while JNK and p38 are more often activated by stress signals and inflammatory cytokines. Activation is tightly regulated by upstream signals and terminated by phosphatases such as dual-specificity phosphatases (DUSPs/MKPs).

Physiological roles of mitogen-activated signaling include cell growth, differentiation, survival, and metabolism. Dysregulation of mitogen-activated pathways is linked to diseases such as cancer, neurodegeneration, and inflammatory disorders. Therapeutic strategies targeting MAPK signaling, including MEK and BRAF inhibitors, illustrate the clinical relevance of mitogen-activated pathways.