PMID- 7730327
OWN - NLM
STAT- MEDLINE
DCOM- 19950601
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 270
IP  - 17
DP  - 1995 Apr 28
TI  - Alternately spliced NH2-terminal immunoglobulin-like Loop I in the ectodomain of 
      the fibroblast growth factor (FGF) receptor 1 lowers affinity for both heparin 
      and FGF-1.
PG  - 10231-5
AB  - Alternate splicing of a single exon encoding an NH2-terminal immunoglobulin (Ig) 
      disulfide loop in the ectodomain of the fibroblast growth factor receptor (FGFR) 
      types 1 and 2 results in alpha and beta isoforms that exhibit 3- and 2-Ig loops, 
      respectively. Previously we demonstrated that alternately spliced Loop I has no 
      independent ligand binding activity but is sufficiently interactive with the 
      ligand- and heparin-binding site formed by Loops II and III to lower affinity for 
      the same fibroblast growth factor (FGF) ligand. Here we show that a lower 
      affinity of FGFR1 alpha for heparin parallels the lower affinity for FGF-1. A 
      mutant of FGFR1 alpha in which the sequence between Loops I and II was deleted 
      exhibits high affinity for both FGF-1 and heparin and other properties of the 
      FGFR1 beta isoform, which include resistance to degradation by trypsin and 
      display of specific antibody epitopes. This suggests that the interloop sequence 
      facilitates the interaction of Loop I with Loops II and III. Lack of expression 
      of both exons coding for Loop I and the sequence between Loops I and II in the 
      FGFR2 gene characterizes rat prostate tumor cells, which exhibit a loss of the 
      low affinity class of FGF receptors. Although the exon coding for the sequence 
      between Loops I and II is alternately spliced in the FGFR2 beta isoform, 
      coordinate expression with the exon coding for Loop I results in the functional 
      differences between the FGFR alpha and FGFR beta variants.
FAU - Wang, F
AU  - Wang F
AD  - Albert B. Alkek Institute of Biosciences and Technology, Department of 
      Biochemistry and Biophysics, Texas A & M University, Houston 77030-3303, USA.
FAU - Kan, M
AU  - Kan M
FAU - Yan, G
AU  - Yan G
FAU - Xu, J
AU  - Xu J
FAU - McKeehan, W L
AU  - McKeehan WL
LA  - eng
GR  - CA59971/CA/NCI NIH HHS/United States
GR  - DK35310/DK/NIDDK NIH HHS/United States
GR  - DK38639/DK/NIDDK NIH HHS/United States
PT  - Journal Article
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 (Antibodies)
RN  - 0 (DNA, Complementary)
RN  - 0 (Immunoglobulins)
RN  - 0 (Receptors, Fibroblast Growth Factor)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - 9005-49-6 (Heparin)
SB  - IM
GS  - FGFR1&agr;
GS  - FGFR1&bgr;
MH  - *Alternative Splicing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies/immunology
MH  - Base Sequence
MH  - Cell Line
MH  - DNA, Complementary
MH  - Fibroblast Growth Factors/*metabolism
MH  - Heparin/*metabolism
MH  - Immunoglobulins/genetics
MH  - Male
MH  - Molecular Sequence Data
MH  - Prostatic Neoplasms/genetics
MH  - Protein Binding
MH  - Rats
MH  - Receptors, Fibroblast Growth Factor/genetics/immunology/*metabolism
EDAT- 1995/04/28 00:00
MHDA- 1995/04/28 00:01
CRDT- 1995/04/28 00:00
PHST- 1995/04/28 00:00 [pubmed]
PHST- 1995/04/28 00:01 [medline]
PHST- 1995/04/28 00:00 [entrez]
AID - S0021-9258(17)47548-X [pii]
AID - 10.1074/jbc.270.17.10231 [doi]
PST - ppublish
SO  - J Biol Chem. 1995 Apr 28;270(17):10231-5. doi: 10.1074/jbc.270.17.10231.