Hepatocyte growth factor and its variant with a deletion of five amino acids are distinguishable in their biological activity and tertiary structure.
A naturally occurring splice variant of hepatocyte growth factor (HGF) lacks a 5-amino acid sequence in the first kringle domain. Comparison of HGF and the deletion variant (dHGF) revealed that the deletion significantly altered the biological activities, solubility, and immunological property of HGF. HGF was respectively about 20-, 10-, and 2-fold more potent than dHGF in the stimulation of DNA synthesis in human umbilical vein endothelial cells, human aorta smooth muscle cells, and NSF-60 (murine myeloblastic cells). Conversely, dHGF was respectively about 3-, 2-, and 2-fold more potent than HGF in the stimulation of DNA synthesis in LLC-PK1 (pig kidney epithelial cells), OK (American opossum kidney epithelial cells), and rat hepatocytes. Moreover, HGF was over 70-fold more soluble than dHGF in PBS. Several monoclonal antibodies raised against dHGF recognized only dHGF and neither HGF nor reduced dHGF, demonstrating that the deletion caused a tertiary structural change. The structural change in HGF may be responsible for its altered biological activities and solubility.
Shima
N
N
Research Institute of Life Science, Snow Brand Milk Products, Co., Ltd., Tochigi, Japan.
Tsuda
E
E
Goto
M
M
Yano
K
K
Hayasaka
H
H
Ueda
M
M
Higashio
K
K
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D017228:Hepatocyte Growth Factor / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology; D006801:Humans; D007120:Immunochemistry; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D017434:Protein Structure, Tertiary; D019859:Proto-Oncogene Proteins c-met; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D017384:Sequence Deletion; D013329:Structure-Activity Relationship
D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D004247:DNA; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases