PMID- 9083085
OWN - NLM
STAT- MEDLINE
DCOM- 19970508
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 272
IP  - 14
DP  - 1997 Apr 4
TI  - Heparin binding and oligomerization of hepatocyte growth factor/scatter factor 
      isoforms. Heparan sulfate glycosaminoglycan requirement for Met binding and 
      signaling.
PG  - 9457-63
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a heparin-binding polypeptide 
      that stimulates cell proliferation, motility, and morphogenesis by activation of 
      its receptor, the c-Met tyrosine kinase. HGF/SF consists of a series of 
      structural units, including an amino-terminal segment with a hairpin loop, four 
      kringle domains, and a serine protease-like region. In this study, we demonstrate 
      that the amino-terminal (N) domain retains the heparin-binding properties of 
      full-length HGF/SF. In contrast to a previous hypothesis, selected basic amino 
      acid residues in the hairpin loop are not critical for heparin binding, although 
      alanine substitution at a subset of these sites markedly reduced the biological 
      activity of the HGF/SF isoform, HGF/NK1. Covalent cross-linking experiments 
      performed with wild-type and heparan sulfate glycosaminoglycan (HSGAG)-deficient 
      Chinese hamster ovary (CHO) cells revealed that Met-HGF/NK1 binding was strongly 
      dependent on HSGAG. Addition of heparin to HSGAG-deficient CHO cells not only 
      restored ligand binding, but also increased ligand-dependent Met tyrosine 
      phosphorylation and c-fos expression. Moreover, our results showed that heparin 
      stimulated ligand oligomerization through an interaction with the N domain. These 
      findings establish the importance of the N domain for heparin-ligand and 
      ligand-ligand interactions, and demonstrate a crucial role for HSGAG in receptor 
      binding and signal transduction.
FAU - Sakata, H
AU  - Sakata H
AD  - Laboratory of Cellular and Molecular Biology, NCI, National Institutes of Health, 
      Bethesda, Maryland 20892, USA.
FAU - Stahl, S J
AU  - Stahl SJ
FAU - Taylor, W G
AU  - Taylor WG
FAU - Rosenberg, J M
AU  - Rosenberg JM
FAU - Sakaguchi, K
AU  - Sakaguchi K
FAU - Wingfield, P T
AU  - Wingfield PT
FAU - Rubin, J S
AU  - Rubin JS
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 9005-49-6 (Heparin)
RN  - 9050-30-0 (Heparitin Sulfate)
RN  - AE28F7PNPL (Methionine)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Circular Dichroism
MH  - Cricetinae
MH  - Heparin/*metabolism
MH  - Heparitin Sulfate/*metabolism
MH  - Hepatocyte Growth Factor/*metabolism
MH  - Methionine/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Molecular Sequence Data
MH  - Protein Conformation
MH  - Proto-Oncogene Proteins c-met
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - *Signal Transduction
MH  - Structure-Activity Relationship
EDAT- 1997/04/04 00:00
MHDA- 1997/04/04 00:01
CRDT- 1997/04/04 00:00
PHST- 1997/04/04 00:00 [pubmed]
PHST- 1997/04/04 00:01 [medline]
PHST- 1997/04/04 00:00 [entrez]
AID - S0021-9258(18)40981-7 [pii]
AID - 10.1074/jbc.272.14.9457 [doi]
PST - ppublish
SO  - J Biol Chem. 1997 Apr 4;272(14):9457-63. doi: 10.1074/jbc.272.14.9457.