Glycosaminoglycan affinity of the complete fibroblast growth factor family.
BACKGROUND
Many fibroblast growth factor family proteins (FGFs) bind to the heparan sulfate/heparin (HP) subtypes of sulfated glycosaminoglycans (GAGs), and a few have recently been reported to also interact with chondroitin sulfate (CS), another sulfated GAG subtype.


METHODS
To gain additional insight into this interaction, we prepared all currently known FGFs (i.e., FGF1-FGF23) and assessed their affinity for HP, CS-B, CS-D and CS-E. In addition, midkine, hepatocyte growth factor and pleiotrophin were studied as other known HP-binding proteins.


RESULTS
We found that members of the FGF19 subfamily (i.e., FGF15, 19, 21 and 23) had little or no affinity for HP; all of the other secretable growth factors tested had strong affinities for HP, as was indicated by the finding that their elution from HP-Sepharose columns required 1.0-1.5 M NaCl. We also found that FGF3, 6, 8 and 22 had strong affinities for CS-E, while FGF5 had a moderate affinity for CS-D. The interactions between FGFs and GAGs thus appear to be more diverse than previously understood.


CONCLUSIONS
This is noteworthy, as the differential interactions of these growth factors with GAGs may be key determinants of their specific biological activities.
Signaling Molecules Research Laboratory, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan.
Masahiro
M
Asada
Michiyo
M
Shinomiya
Masashi
M
Suzuki
Emi
E
Honda
Rika
R
Sugimoto
Masahiko
M
Ikekita
Toru
T
Imamura
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D002809:Chondroitin Sulfates / Q000737:chemistry; D003871:Dermatan Sulfate / Q000737:chemistry; D005346:Fibroblast Growth Factors / Q000737:chemistry* / Q000302:isolation & purification; D006025:Glycosaminoglycans / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry; D008969:Molecular Sequence Data; D011994:Recombinant Proteins
D006025:Glycosaminoglycans; D011994:Recombinant Proteins; C038142:chondroitin sulfate glycosaminoglycan; D003871:Dermatan Sulfate; C065068:chondroitin sulfate D; D005346:Fibroblast Growth Factors; D006493:Heparin; D002809:Chondroitin Sulfates