HFG is synthesized as a preproprotein of 728 amino acids, having a molecular of 84 kDa and containing a 31 amino acid–long signal peptide, which is released from the mature, inactive form (pro-HGF). Activation of HGF occurs by proteolytic cleavage of a single peptide bond between Arg494 and Val495. Theα-chains and β-chains of human HGF consist of 463 and 234 amino acids, respectively. The predicted molecular weight of the α-chains and β-chains are 54 kDa and 26 kDa. The a-chain contains four kringle domains, whereas the β-chain contains a serine protease-like structure (however, without proteolytic activity). Furthermore, HGF displays a structural homology with plasminogen, which is a heterodimeric serine protease containing five kringle domains.(figure 1)
Pro-HGF is proteolytically activated in response to tissue injury. Strikingly, the enzymatic activity leading to pro-HGF conversion into HGF is triggered only in the injured tissues. Thus, the proteolytic activation system functions in vivo as a regulatory mechanism for targeting HGF actions to injured tissues. Several proteases are known to be involved in the activation of pro-HGF, such as HGF activator (HGFA), urokinase-type plasminogen activator (uPA), plasma kallikrein, coagulation factors XI and XII, TMPRSS13 (transmembrane protease serine S1 member 13, a type II transmembrane serine protease), matriptase, and hepsin.
figure1: Pro-HGF and Mature HGF (Photocredit:Toshikazu NAKAMURA, et.al,2010)