The Cysteine Residue Responsible for the Release of Fibroblast Growth Factor-1 Resides in a Domain Independent of the Domain for Phosphatidylserine Binding

• Published in: The Journal of biological chemistry Vol. 270; no. 49; pp. 29039 - 29042
• Main Authors: Tarantini, Francesca, Gamble, Susan, Jackson, Anthony, Maciag, Thomas
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 08.12.1995
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.49.29039

Fibroblast growth factor (FGF)-1 lacks a classical signal sequence to direct its secretion yet utilizes high affinity cell surface receptors to signal its heparin-dependent angiogenic and neurotrophic activities. We have previously reported that FGF-1 is released in response to temperature stress as a latent homodimer through a pathway that is potentiated by the Golgi inhibitor, brefeldin A (Jackson, A., Tarantini, F., Gamble, S., Friedman, S., and Maciag, T.(1995) J. Biol. Chem. 270, 33-36). In an attempt to further characterize this unconventional secretion mechanism, we sought to define the Cys residue(s) critical for FGF-1 dimer formation and release and to determine whether FGF-1 can associate with known phospholipid components of organelle or plasma membranes, which may be disturbed by brefeldin A. Utilizing FGF-1 Cys mutants, we were able to demonstrate that residue Cys is critical for FGF-1 release in response to heat shock. In addition, using solid phase phospholipid binding assays we demonstrate that FGF-1 is able to specifically associate with phosphatidylserine (PS). Heparin inhibits the association between FGF-1 and PS, and synthetic peptide competition assays suggest that the PS-binding domain of FGF-1 lies between residues 114 and 137. These observations indicate that FGF-1 may be able to associate with the PS component of organelle and/or plasma membranes and that the domains responsible for FGF-1 homodimer formation and PS binding are structurally distinct.