Liu Cassie J, Jones Douglas S, Tsai Ping-Chuan, Venkataramana Abhishek, Cochran Jennifer R
Department of Chemical Engineering, Stanford University, Stanford, CA, United States.
Department of Bioengineering, Stanford University, Stanford, CA, United States.
FEBS Lett. 2014 Dec 20;588(24):4831-7. doi: 10.1016/j.febslet.2014.11.018. Epub 2014 Nov 21.
Hepatocyte growth factor (HGF), through activation of the c-MET receptor, mediates biological processes critical for tissue regeneration; however, its clinical application is limited by protein instability and poor recombinant expression. We previously engineered an HGF fragment (eNK1) that possesses increased stability and expression yield and developed a c-MET agonist by coupling eNK1 through an introduced cysteine residue. Here, we further characterize this eNK1 dimer and show it elicits significantly greater c-MET activation, cell migration, and proliferation than the eNK1 monomer. The efficacy of the eNK1 dimer was similar to HGF, suggesting its promise as a c-MET agonist.
肝细胞生长因子（HGF）通过激活c-MET受体，介导对组织再生至关重要的生物学过程；然而，其临床应用受到蛋白质不稳定性和重组表达不佳的限制。我们之前设计了一种具有更高稳定性和表达产量的HGF片段（eNK1），并通过引入的半胱氨酸残基将eNK1偶联，开发了一种c-MET激动剂。在此，我们进一步表征了这种eNK1二聚体，并表明它比eNK1单体引发显著更强的c-MET激活、细胞迁移和增殖。eNK1二聚体的功效与HGF相似，表明其作为c-MET激动剂的前景。
