PMID- 10574949
OWN - NLM
STAT- MEDLINE
DCOM- 20000203
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 49
DP  - 1999 Dec 3
TI  - Mapping ligand binding domains in chimeric fibroblast growth factor receptor
      molecules. Multiple regions determine ligand binding specificity.
PG  - 34785-94
AB  - Fibroblast growth factors (FGFs) mediate essential cellular functions by
      activating one of four alternatively spliced FGF receptors (FGFRs). To determine 
      the mechanism regulating ligand binding affinity and specificity, soluble FGFR1
      and FGFR3 binding domains were compared for activity. FGFR1 bound well to FGF2
      but poorly to FGF8 and FGF9. In contrast, FGFR3 bound well to FGF8 and FGF9 but
      poorly to FGF2. The differential ligand binding specificity of these two
      receptors was exploited to map specific ligand binding regions in mutant and
      chimeric receptor molecules. Deletion of immunoglobulin-like (Ig) domain I did
      not effect ligand binding, thus localizing the binding region(s) to the distal
      two Ig domains. Mapping studies identified two regions that contribute to FGF
      binding. Additionally, FGF2 binding showed positive cooperativity, suggesting the
      presence of two binding sites on a single FGFR or two interacting sites on an
      FGFR dimer. Analysis of FGF8 and FGF9 binding to chimeric receptors showed that a
      broad region spanning Ig domain II and sequences further N-terminal determines
      binding specificity for these ligands. These data demonstrate that multiple
      regions of the FGFR regulate ligand binding specificity and that these regions
      are distinct with respect to different members of the FGF family.
FAU - Chellaiah, A
AU  - Chellaiah A
AD  - Department of Molecular Biology, Washington University School of Medicine, St.
      Louis, Missouri 63110, USA.
FAU - Yuan, W
AU  - Yuan W
FAU - Chellaiah, M
AU  - Chellaiah M
FAU - Ornitz, D M
AU  - Ornitz DM
LA  - eng
GR  - CA60673/CA/NCI NIH HHS/United States
GR  - HD35692/HD/NICHD NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Receptors, Fibroblast Growth Factor)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - EC 2.7.10.1 (FGFR1 protein, human)
RN  - EC 2.7.10.1 (FGFR2 protein, human)
RN  - EC 2.7.10.1 (FGFR3 protein, human)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 2)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 3)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding, Competitive
MH  - COS Cells
MH  - Fibroblast Growth Factors/metabolism
MH  - Humans
MH  - Kinetics
MH  - Molecular Sequence Data
MH  - Point Mutation
MH  - Protein Binding
MH  - *Protein-Tyrosine Kinases
MH  - Receptor Protein-Tyrosine Kinases/genetics/metabolism
MH  - Receptor, Fibroblast Growth Factor, Type 1
MH  - Receptor, Fibroblast Growth Factor, Type 2
MH  - Receptor, Fibroblast Growth Factor, Type 3
MH  - Receptors, Fibroblast Growth Factor/*genetics/*metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - Recombinant Proteins/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Substrate Specificity
EDAT- 1999/11/27 00:00
MHDA- 1999/11/27 00:01
CRDT- 1999/11/27 00:00
PHST- 1999/11/27 00:00 [pubmed]
PHST- 1999/11/27 00:01 [medline]
PHST- 1999/11/27 00:00 [entrez]
AID - 10.1074/jbc.274.49.34785 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Dec 3;274(49):34785-94. doi: 10.1074/jbc.274.49.34785.