Disease relevance of Genes, fms

• The v-fms oncogene product of the McDonough strain of feline sarcoma virus is a member of the receptor tyrosine kinase family [1].
• The data provide evidence for the existence of an active M-CSF/receptor loop in these endometrial cancer cells and suggests the possibility of such activity in tumours of the endometrium and ovary that aberrantly express M-CSF and fms genes [2].
• DNA regions homologous to fms genes were found in Micromonospora sp. SF-2098 and Dactylosporangium matsuzakiense, both producers of fortimicin group antibiotics [3].

High impact information on Genes, fms

• A 5' untranslated exon of the human CSF-1 receptor gene (c-fms) is separated by a 26 kb intron from the 32 kb receptor coding sequences [4].
• Like the v-fms oncogene product, receptors bearing the activating mutation retained high-affinity binding sites for CSF-1 but were retarded in transport to the cell surface and were phosphorylated on tyrosine in the absence of ligand [5].
• Forty C-terminal amino acids of the normal receptor are replaced by 11 unrelated residues in the feline v-fms oncogene product, deleting a C-terminal tyrosine residue (Tyr969) whose phosphorylation might negatively regulate the receptor kinase activity [6].
• The v-fms oncogene induces factor independence and tumorigenicity in CSF-1 dependent macrophage cell line [7].
• Similar to other tyrosine kinase oncogenes (erbB, src, fps, sea), the v-fms oncogene induced progenitor cells to self-renew in an erythropoietin-independent manner [8].

Biological context of Genes, fms

• The COOH-terminal 40 amino acids of the c-fms gene product are replaced in the v-fms gene product by 11 amino acids encoded by the retroviral genome [9].
• Tyrosine autophosphorylation of the v-Fms oncogene product results in the formation of high affinity binding sites for cellular proteins with Src homology 2 (SH2) domains that are involved in various signal cascades [10].
• CSF-1 treatment also increased both the number and size of foci that arose from fibroblasts following transfection with the v-fms oncogene [11].
• A fragment of the v-fms gene encoding a major portion of the extracellular amino terminal domain, the membrane-spanning segment, and the entire carboxyl terminal tyrosine kinase domain of the glycoprotein was molecularly cloned into an inducible prokaryotic expression plasmid [12].
• We show that, similar to the mouse gene, the human c-FMS gene possesses a promoter and an intronic enhancer element (c-fms intronic regulatory element or FIRE) [13].

Anatomical context of Genes, fms

• Although SM-FeSV-transformed fibroblast lines were found to secrete CSF-1, the growth of transformed cells was not affected by antibodies to the v-fms gene product or to the growth factor [14].
• By contrast, the C-terminally truncated glycoprotein encoded by the v-fms oncogene is partially inhibited in its transport to the plasma membrane, is constitutively phosphorylated on tyrosine, and is relatively refractory to both ligand-induced and phorbol ester-induced down-modulation [15].
• NIH 3T3 cells stably transformed by the feline v-fms oncogene or by a mutated, oncogenic human c-fms gene were able to proliferate in the absence of exogenous growth factors [16].
• Specific binding of the mononuclear phagocyte colony-stimulating factor CSF-1 to the product of the v-fms oncogene [14].
• The v-fms oncogene induces factor-independent growth and transformation of the interleukin-3-dependent myeloid cell line FDC-P1 [17].

Associations of Genes, fms with chemical compounds

• The mature protein product of the v-fms gene (gp140fms) is found on the surface of transformed cells; this glycoprotein has external, transmembrane, and cytoplasmic domains [18].
• These results demonstrate the necessity of carbohydrate processing for cell surface expression of the v-fms gene product and illustrate the unique ability to modulate the transformed state of SM-FRE cells with the glycosylational-processing inhibitors CA and MdN [19].

Gene context of Genes, fms

• The v-fms oncogene product has undergone genetic alterations which constitutively activate the receptor kinase in the absence of CSF 1 [20].
• By contrast, the mature cell surface glycoprotein encoded by the v-fms oncogene was phosphorylated on tyrosine in the absence of CSF-1, suggesting that it functions as a ligand-independent kinase [21].
• The c-FMS gene encodes the macrophage colony-stimulating factor receptor (M-CSFR or CSF1-R), which is a tyrosine kinase growth factor receptor essential for macrophage development [13].
• Expression of the v-fms gene product does not transmodulate the normal receptors for CSF-1 or IL-3 and affects neither their affinity, number, nor potential to be independently down-regulated by their ligands or by phorbol esters [22].
• Thus, the synthesis of high levels of the v-fms gene product in FDC-P1 cells abrogated their requirement for IL-3 and rendered the cells tumorigenic by a nonautocrine mechanism [17].

References