PMID- 8662798
OWN - NLM
STAT- MEDLINE
DCOM- 19960815
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 271
IP  - 22
DP  - 1996 May 31
TI  - Hepatocyte growth factor (HGF)/NK1 is a naturally occurring HGF/scatter factor 
      variant with partial agonist/antagonist activity.
PG  - 13110-5
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) stimulates cell proliferation, 
      motility, and morphogenesis by activation of its receptor, the c-Met tyrosine 
      kinase. HGF/SF is structurally related to plasminogen, including an 
      amino-terminal hairpin loop, four kringle domains, and a serine protease-like 
      region. A truncated HGF/SF isoform, designated HGF/NK2, which extends through the 
      second kringle domain and behaves as a competitive HGF/SF antagonist, was 
      previously shown to be encoded by an alternative HGF/SF transcript. In this 
      study, we describe a second naturally occurring HGF/SF variant, HGF/NK1, 
      consisting of the HGF/SF amino-terminal sequence and first kringle domain. This 
      product is encoded by a 2-kilobase alternative transcript containing intronic 
      sequence that was contiguous with exon K1b. Analysis of baculovirus-expressed 
      HGF/NK1 revealed that this isoform possesses the heparin binding properties of 
      HGF/SF and modest mitogenic and scattering activity relative to HGF/SF. However, 
      at a 40-fold molar excess, HGF/NK1 inhibited HGF/SF-dependent DNA synthesis. 
      HGF/NK1 stimulated tyrosine phosphorylation of Met, and covalent affinity 
      cross-linking demonstrated a direct HGF/NK1-receptor interaction. These findings 
      establish that the HGF/SF gene encodes multiple alternative products, which 
      include not only a mitogenic agonist (HGF/SF) and a pure antagonist (HGF/NK2) but 
      also a molecule with partial agonist/antagonist properties.
FAU - Cioce, V
AU  - Cioce V
AD  - Laboratory of Cellular and Molecular Biology, National Cancer Institute, National 
      Institutes of Health, Bethesda, Maryland 20892, USA.
FAU - Csaky, K G
AU  - Csaky KG
FAU - Chan, A M
AU  - Chan AM
FAU - Bottaro, D P
AU  - Bottaro DP
FAU - Taylor, W G
AU  - Taylor WG
FAU - Jensen, R
AU  - Jensen R
FAU - Aaronson, S A
AU  - Aaronson SA
FAU - Rubin, J S
AU  - Rubin JS
LA  - eng
SI  - GENBANK/U46010
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Complementary)
RN  - 0 (Recombinant Proteins)
RN  - 42HK56048U (Tyrosine)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - AE28F7PNPL (Methionine)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Baculoviridae/genetics
MH  - Base Sequence
MH  - Cell Line
MH  - Cloning, Molecular
MH  - DNA Primers
MH  - DNA, Complementary
MH  - Hepatocyte Growth Factor/agonists/antagonists & inhibitors/*metabolism
MH  - Humans
MH  - Methionine/metabolism
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Protein Binding
MH  - Recombinant Proteins/genetics/metabolism
MH  - Spodoptera
MH  - Tyrosine/metabolism
EDAT- 1996/05/31 00:00
MHDA- 1996/05/31 00:01
CRDT- 1996/05/31 00:00
PHST- 1996/05/31 00:00 [pubmed]
PHST- 1996/05/31 00:01 [medline]
PHST- 1996/05/31 00:00 [entrez]
AID - S0021-9258(18)41478-0 [pii]
AID - 10.1074/jbc.271.22.13110 [doi]
PST - ppublish
SO  - J Biol Chem. 1996 May 31;271(22):13110-5. doi: 10.1074/jbc.271.22.13110.