Human macrophage-colony stimulating factor: Alternative RNA and protein processing from a single gene

Rescue of the colony-stimulating factor 1 (CSF-1)–nullizygous mouse (Csf1op/Csf1op) phenotype with a CSF-1 transgene and identification of sites of local CSF-1 synthesis

“…13 Consistent with our observation of cell-surface expression in Csf1 op /Csf1 op ; TgC/ϩ fibroblasts, others have demonstrated cell-surface expression in COS-7 cells expressing full-length CSF-1 cDNA. 11 Whether the surface expression is due to a membrane-spanning or membrane-associated CSF-1 remains to be established.…”

“…6 Complementary DNA (cDNA) clones encoding several different isoforms of both mouse and human CSF-1 have been obtained. [7][8][9][10][11][12] Full-length CSF-1 cDNAs direct the expression of both secreted glycoprotein 13,14 and proteoglycan 15,16 forms, whereas the membrane-bound cell-surface form is derived from a truncated messenger RNA (mRNA) precursor in which the glycosaminoglycan addition site and the proteolytic cleavage sites yielding the secreted forms have been spliced out. 17 The N-terminal 152 amino acids of CSF-1 are required for in vitro biological activity.…”

Molecular identification of COL6A3‐CSF1 fusion transcripts in tenosynovial giant cell tumors

“…In all cases, the breakpoints in CSF1 appear downstream of exon 5 which indicates that the first 649 bp part of CSF1 is not included in a putative COL6A3-CSF1 fusion gene. This part codes for the N-terminal receptor-binding domain which is conserved in all of the three CSF1 mRNA splicing variants, the short (a), long (b), and intermediate (g) forms, that have been isolated (Cerretti et al, 1988;Kawasaki and Ladner, 1990). Deletion studies have shown that bioactivity is fully retained in the first 150 amino acids of mature CSF1 and that the unique four-helical three-dimensional structure of this region interacts with the receptor CSF1R (Kawasaki and Ladner, 1990).…”

Incomplete restoration of colony-stimulating factor 1 (CSF-1) function in CSF-1–deficient Csf1op/Csf1op mice by transgenic expression of cell surface CSF-1

“…[1][2][3][4][5][6] All effects of CSF-1 are mediated by a high-affinity receptor tyrosine kinase 7-10 encoded by the c-fms proto-oncogene. 11 At least 5 mature human or mouse CSF-1 mRNAs (4.0 kb, 3.0 kb, 2.3 kb, 1.9 kb, and 1.6 kb) resulting from alternative splicing in exon 6 and the alternative usages of the 3Ј-untranslated region exons 9 and 10, [12][13][14][15][16][17][18] have been shown to encode 3 isoforms of the CSF-1 protein: a secreted glycoprotein, 19-21 a secreted proteoglycan, 22,23 and a biologically active membrane-spanning cell surface glycoprotein 18,[24][25][26][27][28][29] (for a review, see Stanley 30 ).The primary source of the circulating proteoglycan and glycoprotein CSF-1 is thought to be the endothelial cells that line the small blood vessels (for a review, see Roth and Stanley 31 ). CSF-1 is also synthesized locally, 32 for example, by osteoblasts 33,34 and by uterine epithelial cells.…”