PMID- 11832492
OWN - NLM
STAT- MEDLINE
DCOM- 20020607
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 16
DP  - 2002 Apr 19
TI  - Differential mitogenic effects of single chain hepatocyte growth factor 
      (HGF)/scatter factor and HGF/NK1 following cleavage by factor Xa.
PG  - 14109-15
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional cytokine 
      that is involved in many normal as well as pathological conditions. HGF/NK1, a 
      splice variant of HGF/SF, has been reported to have either antagonistic or 
      agonistic effects with regard to c-Met signaling depending on the cell type. In 
      these experiments, we have determined that HGF/NK1 is a potent mitogen for rat 
      hepatocytes in culture. Furthermore, we have found that coagulation factor Xa 
      (fXa) is capable of cleaving HGF/NK1 and single chain HGF/SF (scHGF/SF). The 
      products resulting from cleavage of HGF/NK1 or scHGF/SF by fXa appear as single 
      bands under non-reducing conditions. The reaction products from the digestion of 
      HGF/NK1 by fXa were separated under reducing conditions, and the cleavage site, 
      as determined by N-terminal sequencing, was located C-terminal to arginine 134. 
      Previous work established that the heparin-binding domain for HGF/SF is located 
      in the N domain of HGF/SF. Additionally, the dimerization of the HGF/SF receptor 
      (c-Met) by the ligand HGF/NK1 is facilitated by heparin and related sulfonated 
      sugars on the cell surface, whereas heparin is not required for HGF/SF-mediated 
      dimerization. Cleavage of single chain HGF/SF or HGF/NK1 by factor Xa does not 
      alter the affinity of the respective molecules for heparin, but it did variably 
      affect the associated mitogenic activity of these factors. The associated 
      mitogenic activity of HGF/NK1 was reduced by more than 90%, whereas the mitogenic 
      activity of scHGF/SF was unaffected. This suggests mandatory maintenance of a 
      steric interaction of the N domain and the first kringle domain for HGF/NK1 to 
      act as an agonist for rat hepatocyte growth but is not required by full-length 
      HGF/SF.
FAU - Pediaditakis, Peter
AU  - Pediaditakis P
AD  - Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, 
      Pennsylvania 15261.
FAU - Monga, Satdarshan P S
AU  - Monga SP
FAU - Mars, Wendy M
AU  - Mars WM
FAU - Michalopoulos, George K
AU  - Michalopoulos GK
LA  - eng
GR  - R01 CA035373/CA/NCI NIH HHS/United States
GR  - CA30241/CA/NCI NIH HHS/United States
GR  - CA35373/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020206
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Ligands)
RN  - 0 (Mitogens)
RN  - 0 (Protein Isoforms)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 9005-49-6 (Heparin)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 3.4.21.6 (Factor Xa)
SB  - IM
MH  - *Alternative Splicing
MH  - Animals
MH  - Arginine/chemistry
MH  - Binding Sites
MH  - Cells, Cultured
MH  - Dimerization
MH  - Dose-Response Relationship, Drug
MH  - Factor Xa/*metabolism
MH  - Heparin/chemistry
MH  - Hepatocyte Growth Factor/*genetics/*metabolism
MH  - Hepatocytes/metabolism
MH  - Ligands
MH  - Male
MH  - *Mitogens
MH  - Models, Molecular
MH  - Protein Binding
MH  - Protein Isoforms
MH  - Protein Structure, Tertiary
MH  - Rats
MH  - Rats, Inbred F344
MH  - Time Factors
PMC - PMC1821081
MID - NIHMS16111
EDAT- 2002/02/08 10:00
MHDA- 2002/06/12 10:01
PMCR- 2008/02/01
CRDT- 2002/02/08 10:00
PHST- 2002/02/08 10:00 [pubmed]
PHST- 2002/06/12 10:01 [medline]
PHST- 2002/02/08 10:00 [entrez]
PHST- 2008/02/01 00:00 [pmc-release]
AID - S0021-9258(19)61016-1 [pii]
AID - 10.1074/jbc.M112196200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Apr 19;277(16):14109-15. doi: 10.1074/jbc.M112196200. Epub 2002 
      Feb 6.