PMID- 18156180
OWN - NLM
STAT- MEDLINE
DCOM- 20080415
LR  - 20220129
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 283
IP  - 9
DP  - 2008 Feb 29
TI  - Interactions of hepatocyte growth factor/scatter factor with various 
      glycosaminoglycans reveal an important interplay between the presence of 
      iduronate and sulfate density.
PG  - 5235-48
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) has a cofactor requirement for 
      heparan sulfate (HS) and dermatan sulfate (DS) in the optimal activation of its 
      signaling receptor MET. However, these two glycosaminoglycans (GAGs) have 
      different sugar backbones and sulfation patterns, with only the presence of 
      iduronate in common. The structural basis for GAG recognition and activation is 
      thus very unclear. We have clarified this by testing a wide array of natural and 
      modified GAGs for both protein binding and activation. Comparisons between 
      Ascidia nigra (2,6-O-sulfated) and mammalian (mainly 4-O-sulfated) DS species, as 
      well as between a panel of specifically desulfated heparins, revealed that no 
      specific sulfate isomer, in either GAG, is vital for interaction and activity. 
      Moreover, different GAGs of similar sulfate density had comparable properties, 
      although affinity and potency notably increase with increasing sulfate density. 
      The weaker interaction with CS-E, compared with DS, shows that GlcA-containing 
      polymers can bind, if highly sulfated, but emphasizes the importance of the 
      flexible IdoA ring. Our data indicate that the preferred binding sites in DS in 
      vivo will be comprised of disulfated, IdoA(2S)-containing motifs. In HS, 
      clustering of N-/2-O-/6-O-sulfation in S-domains will lead to strong reactivity, 
      although binding can also be mediated by the transition zones where sulfates are 
      mainly at the N- and 6-O- positions. GAG recognition of HGF/SF thus appears to be 
      primarily driven by electrostatic interactions and exhibits an interesting 
      interplay between requirements for iduronate and sulfate density that may reflect 
      in part a preference for particular sugar chain conformations.
FAU - Catlow, Krista R
AU  - Catlow KR
AD  - Cancer Research UK Glyco-Oncology Group, School of Cancer and Imaging Sciences, 
      Paterson Institute for Cancer Research, University of Manchester, Manchester M20 
      4BX, United Kingdom.
FAU - Deakin, Jon A
AU  - Deakin JA
FAU - Wei, Zheng
AU  - Wei Z
FAU - Delehedde, Maryse
AU  - Delehedde M
FAU - Fernig, David G
AU  - Fernig DG
FAU - Gherardi, Ermanno
AU  - Gherardi E
FAU - Gallagher, John T
AU  - Gallagher JT
FAU - Pavao, Mauro S G
AU  - Pavao MS
FAU - Lyon, Malcolm
AU  - Lyon M
LA  - eng
GR  - G0800025/MRC_/Medical Research Council/United Kingdom
GR  - CRUK_/Cancer Research UK/United Kingdom
GR  - R03TW05775/TW/FIC NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20071221
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Glycosaminoglycans)
RN  - 0 (HGF protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Growth Factor)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Sulfates)
RN  - 0 (glucosaminoglycans)
RN  - 3402-98-0 (Iduronic Acid)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (MET protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Animals
MH  - Carbohydrate Conformation
MH  - Glycosaminoglycans/*chemistry/metabolism
MH  - Hepatocyte Growth Factor/*chemistry/metabolism
MH  - Humans
MH  - Iduronic Acid/*chemistry/metabolism
MH  - Protein Binding
MH  - Proto-Oncogene Proteins
MH  - Proto-Oncogene Proteins c-met
MH  - Receptors, Growth Factor
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Species Specificity
MH  - Sulfates/*chemistry/metabolism
MH  - Urochordata/*chemistry/metabolism
EDAT- 2007/12/25 09:00
MHDA- 2008/04/16 09:00
CRDT- 2007/12/25 09:00
PHST- 2007/12/25 09:00 [pubmed]
PHST- 2008/04/16 09:00 [medline]
PHST- 2007/12/25 09:00 [entrez]
AID - S0021-9258(20)57243-8 [pii]
AID - 10.1074/jbc.M706589200 [doi]
PST - ppublish
SO  - J Biol Chem. 2008 Feb 29;283(9):5235-48. doi: 10.1074/jbc.M706589200. Epub 2007 
      Dec 21.