TY - JOUR
T1 - Ligand binding properties of binary complexes of heparin and immunoglobulin-like modules of FGF receptor 2
AU - Uematsu, Fumiyuki
AU - Kan, Mikio
AU - Wang, Fen
AU - Jang, Jun Hyeog
AU - Luo, Yongde
AU - McKeehan, Wallace L.
N1 - Funding Information:
This work was supported by Public Health Service Grants DK35310 and DK47039 from the National Institute of Diabetes and Digestive and Kidney Diseases and Grant CA59971 from the National Cancer Institute.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2000/6/16
Y1 - 2000/6/16
N2 - Epithelial cells, which express FGFR2IIIb, bind and respond to FGF-1, FGF-7 and FGF-10, but not FGF-2. Stromal cells, which bind and respond to FGF-1 and FGF-2, but not FGF-7 and FGF-10, express FGFR2IIIc or FGFR1IIIc. Here we show that when both isolated FGFR2βIIIb and FGFR2βIIIc or their common Ig module II are allowed to affinity select heparin from a mixture, the resultant binary complexes bound FGF-1, FGF-2, and FGF-7 with nearly equal affinity. In addition, FGF-2 and FGF-7 bound to both heparin-Ig module IIIb and IIIc complexes, but FGF-1 bound to neither Ig module III. The results show that in isolation both Ig modules II and III of FGFR2 can interact with heparin and that each exhibits a binding site for FGF. We suggest that the specificity of FGFR2IIIb and FGFR2IIIc is dependent on the cell membrane environment and heparin/heparan sulfate. Ig modules II and III cooperate both within monomers and across dimers with cellular heparan sulfates to confer cell type-dependent specificity of the FGFR complex for FGF. (C) 2000 Academic Press.
AB - Epithelial cells, which express FGFR2IIIb, bind and respond to FGF-1, FGF-7 and FGF-10, but not FGF-2. Stromal cells, which bind and respond to FGF-1 and FGF-2, but not FGF-7 and FGF-10, express FGFR2IIIc or FGFR1IIIc. Here we show that when both isolated FGFR2βIIIb and FGFR2βIIIc or their common Ig module II are allowed to affinity select heparin from a mixture, the resultant binary complexes bound FGF-1, FGF-2, and FGF-7 with nearly equal affinity. In addition, FGF-2 and FGF-7 bound to both heparin-Ig module IIIb and IIIc complexes, but FGF-1 bound to neither Ig module III. The results show that in isolation both Ig modules II and III of FGFR2 can interact with heparin and that each exhibits a binding site for FGF. We suggest that the specificity of FGFR2IIIb and FGFR2IIIc is dependent on the cell membrane environment and heparin/heparan sulfate. Ig modules II and III cooperate both within monomers and across dimers with cellular heparan sulfates to confer cell type-dependent specificity of the FGFR complex for FGF. (C) 2000 Academic Press.
KW - Cell communication
KW - Extracellular matrix
KW - Heparan sulfate proteoglycans
KW - Prostate cancer
KW - Stromal-epithelial interactions
KW - Tyrosine kinases
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U2 - 10.1006/bbrc.2000.2872
DO - 10.1006/bbrc.2000.2872
M3 - Article
C2 - 10860838
AN - SCOPUS:0034674223
VL - 272
SP - 830
EP - 836
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -