PMID- 7756992
OWN - NLM
STAT- MEDLINE
DCOM- 19950626
LR  - 20181113
IS  - 0961-8368 (Print)
IS  - 1469-896X (Electronic)
IS  - 0961-8368 (Linking)
VI  - 3
IP  - 12
DP  - 1994 Dec
TI  - Molecular evolution and domain structure of plasminogen-related growth factors 
      (HGF/SF and HGF1/MSP).
PG  - 2378-94
AB  - Plasminogen-related growth factors, a new family of polypeptide growth factors 
      with the basic domain organization and mechanism of activation of the blood 
      proteinase plasminogen, include hepatocyte growth factor/scatter factor (HGF/SF), 
      a potent effector of the growth, movement, and differentiation of epithelia and 
      endothelia, and hepatocyte growth factor-like/macrophage stimulating protein 
      (HGF1/MSP), an effector of macrophage chemotaxis and phagocytosis. Phylogeny of 
      the serine proteinase domains and analysis of intron-exon boundaries and kringle 
      sequences indicate that HGF/SF, HGF1/MSP, plasminogen, and apolipoprotein (a) 
      have evolved from a common ancestral gene that consisted of an N-terminal domain 
      corresponding to plasminogen activation peptide (PAP), 3 copies of the kringle 
      domain, and a serine proteinase domain. Models of the N domains of HGF/SF, 
      HGF1/MSP, and plasminogen, characterized by the presence of 4 conserved Cys 
      residues forming a loop in a loop, have been modeled based on disulfide-bond 
      constraints. There is a distinct pattern of charged and hydrophobic residues in 
      the helix-strand-helix motif proposed for the PAP domain of HGF/SF; these may be 
      important for receptor interaction. Three-dimensional structures of the 4 kringle 
      and the serine proteinase domains of HGF/SF were constructed by comparative 
      modeling using the suite of programs COMPOSER and were energy minimized. Docking 
      of a lysine analogue indicates a putative lysine-binding pocket within kringle 2 
      (and possibly another in kringle 4). The models suggest a mechanism for the 
      formation of a noncovalent HGF/SF homodimer that may be responsible for the 
      activation of the Met receptor. These data provide evidence for the divergent 
      evolution and structural similarity of plasminogen, HGF/SF, and HGF1/MSP, and 
      highlight a new strategy for growth factor evolution, namely the adaptation of a 
      proteolytic enzyme to a role in receptor activation.
FAU - Donate, L E
AU  - Donate LE
AD  - Department of Crystallography, Birkbeck College, University of London, United 
      Kingdom.
FAU - Gherardi, E
AU  - Gherardi E
FAU - Srinivasan, N
AU  - Srinivasan N
FAU - Sowdhamini, R
AU  - Sowdhamini R
FAU - Aparicio, S
AU  - Aparicio S
FAU - Blundell, T L
AU  - Blundell TL
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Protein Sci
JT  - Protein science : a publication of the Protein Society
JID - 9211750
RN  - 0 (Apolipoproteins A)
RN  - 0 (Growth Substances)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (macrophage stimulating protein)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 9001-26-7 (Prothrombin)
RN  - 9001-30-3 (Factor XII)
RN  - 9001-91-6 (Plasminogen)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 3.4.21.- (Plasminogen Activators)
RN  - EC 3.4.21.- (Serine Endopeptidases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Apolipoproteins A/chemistry/genetics
MH  - *Biological Evolution
MH  - Computer Simulation
MH  - Factor XII/chemistry/genetics
MH  - Genes
MH  - Growth Substances/*chemistry/genetics
MH  - Hepatocyte Growth Factor/*chemistry/genetics
MH  - *Kringles
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Multigene Family
MH  - Phylogeny
MH  - Plasminogen/*chemistry/genetics
MH  - Plasminogen Activators/chemistry/genetics
MH  - *Protein Structure, Tertiary
MH  - Prothrombin/chemistry/genetics
MH  - *Proto-Oncogene Proteins
MH  - Proto-Oncogene Proteins c-met
MH  - Receptor Protein-Tyrosine Kinases/chemistry
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Serine Endopeptidases/chemistry/genetics
PMC - PMC2142779
EDAT- 1994/12/01 00:00
MHDA- 1994/12/01 00:01
PMCR- 1995/06/01
CRDT- 1994/12/01 00:00
PHST- 1994/12/01 00:00 [pubmed]
PHST- 1994/12/01 00:01 [medline]
PHST- 1994/12/01 00:00 [entrez]
PHST- 1995/06/01 00:00 [pmc-release]
AID - 10.1002/pro.5560031222 [doi]
PST - ppublish
SO  - Protein Sci. 1994 Dec;3(12):2378-94. doi: 10.1002/pro.5560031222.