Hepatopoietin A: partial characterization and trypsin activation of a hepatocyte growth factor.
Rat hepatocytes in primary culture are stimulated to synthesize DNA by high-molecular-weight fractions from rat serum. This activity has been previously given the name hepatopoietin A (HPTA). HPTA, with an apparent molecular weight of 150,000 to 250,000, stimulated the incorporation of [3H]thymidine into DNA, quantitated by autoradiography as percentage of nuclear labeling. Properties of HPTA include: sensitivity to heat; stability in minimal essential media at 4 degrees C; in lyophilized form; or in 25% glycerol at -20 degrees C; and instability at 4 degrees C in isotonic buffer. Trypsin digestion of HPTA resulted in an increase in biological activity. Both the trypsinized and native forms of this activity were not inhibited by antiserum against mouse epidermal growth factor in this bioassay. Treatment of HPTA with trypsin resulted in a shift of its apparent molecular weight on a Sephadex G-50 column to less than 6000. This trypsinized HPTA activity did not comigrate with 125I-labeled epidermal growth factor on the same column. These results demonstrate that HPTA exists in normal serum as a large precursor to a more active moiety, generated by proteolytic cleavage, which is not identical to epidermal growth factor. Fractions from human serum and plasma of molecular weight similar to that of HPTA have also been shown to stimulate DNA synthesis in rat hepatocytes.
Thaler
F J
FJ
Michalopoulos
G K
GK
D000818:Animals; D001798:Blood Proteins / Q000302:isolation & purification* / Q000494:pharmacology; D002478:Cells, Cultured; D002845:Chromatography; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000378:metabolism; D006133:Growth Substances / Q000302:isolation & purification*; D017228:Hepatocyte Growth Factor; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014357:Trypsin / Q000494:pharmacology*
D001798:Blood Proteins; D006133:Growth Substances; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D004247:DNA; D014357:Trypsin