Identification and characterization of an intracellular protein complex that binds fibroblast growth factor-2 in bovine brain

Abstract

The fibroblast growth factor (FGF) family is composed of polypeptides with sequence identity which signal through transmembrane tyrosine kinase receptors. We report here the purification from bovine brain microsomes of an FGF-2-binding complex composed of three proteins of apparent molecular masses 150 kDa, 79 kDa and 46 kDa. Only the 150 kDa and 79 kDa proteins bound FGF-2 in cross-linking and ligandblotting experiments. Binding of FGF-2 to p79 is enhanced in the presence of calcium. Peptide sequences allowed the identification of p150 and the cloning of the cDNAs encoding p79 and p46. The deduced amino acid sequence of p79 reveals high similarity to those of gastrin-binding protein and mitochondrial enoyl-

Binding sites for progastrin‐derived peptides in colonic crypts

“…However, sequence comparisons have revealed that the 78 kDa gastrin‐binding protein (or gastrin/CCK‐C receptor) is closely related to a family of mitochondrial proteins involved in fatty acid oxidation 17 . The question of how a mitochondrial protein may appear at the cell surface has been answered by a recent report that two mRNA, differing only in the signal sequence they encode, exist for the 78 kDa gastrin‐binding protein 34 . One signal sequence targets the protein to the endoplasmic reticulum, and hence presumably to the cell surface, while the other targets the protein to the mitochondria 34 …”

“…17 The question of how a mitochondrial protein may appear at the cell surface has been answered by a recent report that two mRNA, differing only in the signal sequence they encode, exist for the 78 kDa gastrin-binding protein. 34 One signal sequence targets the protein to the endoplasmic reticulum, and hence presumably to the cell surface, while the other targets the protein to the mitochondria. 34 The receptor binding data presented herein have significant implications for our understanding of the mechanism by which gastrin 17 gly stimulates growth of the colonic mucosa.…”

“…34 One signal sequence targets the protein to the endoplasmic reticulum, and hence presumably to the cell surface, while the other targets the protein to the mitochondria. 34 The receptor binding data presented herein have significant implications for our understanding of the mechanism by which gastrin 17 gly stimulates growth of the colonic mucosa. The inability to detect the binding characteristic of CCK-A and gastrin/CCK-B receptors suggests that it is unlikely that either receptor is involved in the hyperplasia observed in the colonic mucosa of transgenic mice overexpressing gastrin 17 gly.…”

“…Progastrin is converted to gastrin 34 gly by cleavage at paired arginine (R) residues by prohormone convertase(s). Amidation of gastrin34 gly is followed by cleavage at the paired lysine (K) residues to yield gastrin 17 ( ). Alternatively, cleavage of gastrin 34 gly at the paired lysine (K) residues results in gastrin 17 gly.…”