Signaling pathways and biological responses induced by Scatter Factors

摘要

Hepatocyte Growth Factor (HGF) and Macrophage Stimulating Protein (MSP) are two closely related glycoproteins, produced by mesenchymal cells and collectively named "Scatter Factors" after their ability to induce dissociation of epithelial colonies and promote migration and invasion of extracellular matrix (for a review, see [1]). Scatter Factors have closely related structural features: they are large molecules (approx. 100 KDa), secreted as single chain precursors which are then activated in the extracellular environment by specific proteases releasing two subunits (60 kD alpha-chain and 30 kD beta-chain), joined by disulfide bonds. Scatter Factors show considerable homology with plasminogen, both in the alpha-chain, which contains four kringle structures, and in the beta-chain, which has 38% sequence identity with the serine protease domain of plasminogen. Hence they are also called Plasminogen-Related Growth Factor (PRGF) -1 and -2, respectively. However, protease activity is lost due to substitution of critical amino acid residues.