HEPATOCYTE GROWTH-FACTOR AND ITS VARIANT WITH A DELETION OF 5 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 sig nificantly altered the biological activities, solubility, and immunolo gical property of HGF. HGF was respectively about 20-, 10-, and 2-fold more potent than dHGF in the stimulation of DNA synthesis in human um bilical vein endothelial cells, human aorta smooth muscle cells, and N SF-60 (murine myeloblastic cells). Conversely, dHGF was respectively a bout 3-, 2-, and 2-fold more potent than HGF in the stimulation of DNA synthesis in LLC-PK1 (pig kidney epithelial cells), OK (American opos sum kidney epithelial cells), and rat hepatocytes. Moreover, HGF was o ver 70-fold more soluble than dHGF in PBS. Several monoclonal antibodi es raised against dHGF recognized only dHGF and neither HGF nor reduce d dHGF, demonstrating that the deletion caused a tertiary structural c hange. The structural change in HGF may be responsible for its altered biological activities and solubility. (C) 1994 Academic Press, Inc.