Predicted structure of human CSF-1R. The extracellular ligand-binding portion is organized into 5 immunoglobulin-like domains, 4 of which are stabilized by disulfide bonds (S-S). All such domains are homologous to sequences of the C2-SET. Positions of asparagine-linked oligosaccharide chains are indicated (0). The intracellular kinase domain (stippled bars) is interrupted by spacer sequences containing 2 predicted sites of receptor phosphorylation at tyrosines (Y) 699 and 708. A third phosphorylation site (Y809) occurs in the distal core consensus sequences. The membrane-proximal kinase segment includes a glycine-rich signature sequence (G-X-G-X-X-G) characteristic of kinases in general. This is followed by the ATP-binding site at lysine (K) 616. The C-terminal tail contains a single tyrosine residue (Y969) whose removal upregulates receptor kinase activity. The data are taken from a previously reported human c-fms complementary DNA sequence. Unpublished information regarding sites of phosphorylation within the murine receptor was provided by Drs P. Tapley, A. Kazlauskas, and L. R. Rohrschneider and was aligned with the human amino acid sequence. Reprinted from Sherr18 with permission.
