HIGH-AFFINITY IMMUNOREACTIVE FGF RECEPTORS IN THE EXTRACELLULAR-MATRIX OF VASCULAR ENDOTHELIAL-CELLS - IMPLICATIONS FOR THE MODULATION OF FGF-2

We recently characterized three FGF-binding proteins (FGF-BPs) which a re soluble forms of the extracellular domains of the high affinity FGF receptors (Hanneken, A. M., W. Ying, N. Ling, and A. Baird. Proc. Nat l. Acad, Sci, USA. 1994. 91:9170-9174). These proteins circulate in bl ood and have been proposed to modulate the biological activity of the FGF family of proteins. Immunohistochemical studies now demonstrate th at these soluble, truncated FGF receptors are also present in the base ment membranes of retinal vascular endothelial cells, These immunoreac tive proteins can be detected with antibodies raised to the extracellu lar domain of FGFR-1 but not with antibodies raised to either the juxt amembrane domain or the cytoplasmic domain of FGFR-1. Western blotting of human retinal extracts with the antibody raised to the extracellul ar domain of FGFR-1 detects specific, low molecular mass proteins at 8 5 kD and 55 kD, corresponding in size to the FGF-BPs, which are not de tected with antibodies against the cytoplasmic domain of the receptor. The interaction of this receptor with the extracellular matrix is not dependent on the presence of FGF-2. Immunoreactive receptors are stil l detected in vascular basement membranes after the removal of FGF-2 w ith heparitinase. In addition, the recombinant extracellular domain of FGFR-1 continues to bind to corneal endothelial cell matrix after end ogenous FGF-2 has been removed with 2 M NaCl. Acid treatment, which ha s been shown to disrupt protein interactions with the extracellular ma trix, leads to a significant reduction in the presence of the matrix f orm of the FGF receptor, This loss can be restored with exogenous incu bations of the recombinant extracellular domain of FGFR-1. This report is the first demonstration that a truncated form of a high affinity g rowth factor receptor can be localized to the extracellular matrix. Th ese findings add to the list of binding proteins associated with the e xtracellular matrix (IGFBP-5) and suggest a potentially new regulatory mechanism for controlling the biological availability of FGF, and oth er peptide growth factors, in the extracellular matrix.