Hepatocyte growth factor (HGF) is critical for tissue homeostasis and repair in many organs including the lung, heart, kidney, liver, nervous system, and skin. HGF is a heterodimeric protein containing 20 disulfide bonds distributed among an amino-terminal hairpin, four kringle domains, and a serine protease-like domain. Due to its complex structure, recombinant production of HGF in prokaryotes requires denaturation and refolding, processes that are impractical for large-scale manufacture. Thus, pharmaceutical quantities of HGF are not available despite its potential applications. A fragment of the Listeria monocytogenes internalin B protein from amino acids 36–321 (InlB_36–321) was demonstrated to bind to and partially activate the HGF receptor Met. InlB_36–321has a stable β-sheet structure and is easily produced in its native conformation by Escherichia coli . We cloned InlB_36–321(1×InlB_36–321) and engineered a head-to-tail repeat of InlB_36–321with a linker peptide (2×InlB_36–321); 1×InlB_36–321and 2×InlB_36–321were purified from E. coli . Both 1× and 2×InlB_36–321activated the Met tyrosine kinase. We subsequently compared signal transduction of the two proteins in primary lung endothelial cells. 2×InlB_36–321activated ERK1/2, STAT3, and phosphatidylinositol 3-kinase/Akt pathways, whereas 1×InlB_36–321activated only STAT3 and ERK1/2. The 2×InlB_36–321promoted improved motility compared with 1×InlB_36–321and additionally stimulated proliferation equivalent to full-length HGF. Both the 1× and 2×InlB_36–321prevented apoptosis by the profibrotic peptide angiotensin II in cell culture and ex vivo lung slice cultures. The ease of large-scale production and capacity of 2×InlB_36–321to mimic HGF make it a potential candidate as a pharmaceutical agent for tissue repair.