mitogens

Mitogens are signaling molecules that stimulate cell division by promoting progression through the cell cycle, particularly the transition from G1 to S phase. They act by transmitting signals that favor DNA synthesis and replication, often in autocrine or paracrine fashion. Mitogens are not identical to nutrients or substrates; they induce proliferation rather than serving as metabolic inputs.

Mechanism: Many mitogens bind to cell-surface receptors such as receptor tyrosine kinases or G protein-coupled receptors, triggering signaling cascades including the MAPK/ERK and PI3K/AKT pathways. These signals boost expression of cyclins D and E, activate CDKs, and lead to phosphorylation and inactivation of the retinoblastoma protein, permitting entry into S phase. The cellular response to a mitogen is integrated with other cues that can promote or restrain division.

Examples and contexts: Classic mitogens include epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and fibroblast growth factors (FGFs), as well as insulin and insulin-like growth factors in many cell types. In cell culture, serum provides a mixture of mitogens that promote proliferation. In development and tissue repair, mitogenic signaling supports growth, though misregulation can contribute to abnormal or excessive cell growth.

Clinical relevance: Mitogenic signaling is a central topic in cancer biology, as constitutive or excessive pathway activation drives uncontrolled proliferation. Therapeutic strategies target these pathways, with inhibitors of EGFR, MEK, or CDKs used to treat certain cancers. Understanding mitogens helps explain how normal growth and regeneration are coordinated with cancer risk when signaling becomes dysregulated.