pleiotrophin

Pleiotrophin (PTN), also known as heparin-binding growth factor 8 (HBGF-8), is a secreted, basic growth factor belonging to the pleiotrophin/midkine family. It is a small protein (~15-16 kDa) rich in basic amino acids and has a strong affinity for heparin and heparan sulfate proteoglycans.

Expression and function: PTN is expressed during embryogenesis in the nervous system and various tissues; in adults it is detected at lower levels but can be induced by injury. PTN stimulates neurite outgrowth, neuronal migration, survival, and synaptic plasticity, and participates in angiogenesis and wound healing. In the developing brain it contributes to neural patterning and tissue organization.

Signaling and receptors: The best characterized receptor is the receptor-type protein tyrosine phosphatase zeta (PTPRZ1/RPTPβ/ζ) on glial and neural cells; PTN binding modulates phosphatase activity and activates downstream signaling pathways including MAPK/ERK and PI3K/AKT in some contexts. PTN also associates with heparan sulfate proteoglycans and can interact with integrins and syndecans to regulate cell adhesion and migration.

Clinical and research relevance: PTN is ectopically expressed in several cancers where it correlates with tumor growth, angiogenesis, and invasiveness, making it a subject of study as a potential therapeutic target or biomarker. In the nervous system, PTN expression is observed in gliomas, neuroblastoma, and brain injury models, where it may participate in regeneration and pathological remodeling.

Genetics and evolution: PTN is part of a conserved growth factor family; genetic disruption in model organisms yields mild phenotypes, supporting partly redundant functions with the related growth factor midkine.