Human CSF-1: gene structure and alternative splicing of mRNA precursors.

Abstract

Bone marrow progenitor cells differentiate into mononuclear phagocytes in the presence of colony stimulating factor‐1 (CSF‐1). Characterization of the human CSF‐1 gene shows that it contains 10 exons and 9 introns, which span 20 kb. Analysis of multiple CSF‐1 transcripts demonstrates that alternate use of exon 6 splice acceptor sites and 3′ noncoding sequence exons occurs. These alternatively spliced transcripts can encode either a 224 or a 522 amino acid CSF‐1. Implications of differential splicing for the production and function of CSF‐1 are discussed.

Cell specific transformation by c-fms activating loop mutations is attributable to constitutive receptor degradation

“…The cells were then washed three times in R10 in order to remove IL-3 before plating in Difco (Detroit, USA) soft agar at concentrations of 1610 6 , 1610 5 , and 1610 4 cells/ml in R10 with or without 5000 U/ml of recombinant human M-CSF with a speci®c activity of 5610 7 units per mg (Ladner et al, 1987;Halenbeck et al, 1989) provided by Chiron (Emeryville, CA, USA). Alternatively 2610 5 washed cells were seeded into 4 mls of R10 with or without 5000 U/ml M-CSF in six well plates.…”

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.…”

Growth Hormone Receptor and Insulin-like Growth Factor-I Immunoreactivity in Osteoclast-like Cells During Tooth Eruption in the Toothless (Osteopetrotic) Rat Following Treatment with Colony-Stimulating Factor-1

“…NIH 86-23, 1985). Four normal and four mutant rats were treated with highly purified recombinant human CSF-1 (Ladner et al, 1987;Halenbeck et al, 1989), which was generously provided by Chiron Corporation. Administration of the growth factor was by subcutaneous injection of 10 6 units every 48 hours (Ralph et al, 1986), beginning at birth for a period of 2 weeks.…”