Stanley E R, Berg K L, Einstein D B, Lee P S, Pixley F J, Wang Y, Yeung Y G
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, New York 10461, USA.
Mol Reprod Dev. 1997 Jan;46(1):4-10. doi: 10.1002/(SICI)1098-2795(199701)46:1<4::AID-MRD2>3.0.CO;2-V.
Colony-stimulating factor-1 (CSF-1), also known as macrophage colony-stimulating factor, controls the survival, proliferation, and differentiation of mononuclear phagocytes and regulates cells of the females reproductive tract. It appears to play an autocrine and/or paracrine role in cancers of the ovary, endometrium, breast, and myeloid and lymphoid tissues. Through alternative mRNA splicing and differential post-translational proteolytic processing, CSF-1 can either be secreted into the circulation as a glycoprotein or chondroitin sulfate-containing proteoglycan or be expressed as a membrane-spanning glycoprotein on the surface of CSF-1-producing cells. Studies with the op/op mouse, which possesses an inactivating mutation in the CSF-1 gene, have established the central role of CSF-1 in directly regulating osteoclastogenesis and macrophage production. CSF-1 appears to preferentially regulate the development of macrophages found in tissues undergoing active morphogenesis and/or tissue remodeling. These CSF-1 dependent macrophages may, via putative trophic and/or scavenger functions, regulate characteristics such as dermal thickness, male fertility, and neural processing. Apart from its expression on mononuclear phagocytes and their precursors, CSF-1 receptor (CSF-1R) expression on certain nonmononuclear phagocytic cells in the female reproductive tract and studies in the op/op mouse indicate that CSF-1 plays important roles in female reproduction. Restoration of circulating CSF-1 to op/op mice has preliminarily defined target cell populations that are regulated either humorally or locally by the synthesis of cell-surface CSF-1 or by sequestration of the CSF-1 proteoglycan. The CSF-1R is a tyrosine kinase encoded by the c-fms proto-oncogene product. Studies by several groups have used cells expressing either the murine or human CSF-1R in fibroblasts to pinpoint the requirement of kinase activity and the importance of various receptor tyrosine phosphorylation sites for signaling pathways stimulated by CSF-1. To investigate post-CSF-1R signaling in the macrophage, proteins that are rapidly phosphorylated on tyrosine in response to CSF-1 have been identified, together with proteins associated with them. Studies on several of these proteins, including protein tyrosine phosphates 1C, the c-cbl proto-oncogene product, and protein tyrosine phosphatase-phi are discussed.
集落刺激因子-1（CSF-1），也称为巨噬细胞集落刺激因子，可控制单核吞噬细胞的存活、增殖和分化，并调节女性生殖道细胞。它似乎在卵巢癌、子宫内膜癌、乳腺癌以及髓系和淋巴组织癌中发挥自分泌和/或旁分泌作用。通过可变mRNA剪接和不同的翻译后蛋白水解加工，CSF-1既可以作为糖蛋白或含硫酸软骨素的蛋白聚糖分泌到循环中，也可以作为跨膜糖蛋白在产生CSF-1的细胞表面表达。对op/op小鼠（其CSF-1基因存在失活突变）的研究确立了CSF-1在直接调节破骨细胞生成和巨噬细胞产生中的核心作用。CSF-1似乎优先调节在经历活跃形态发生和/或组织重塑的组织中发现的巨噬细胞的发育。这些依赖CSF-1的巨噬细胞可能通过假定的营养和/或清除功能，调节诸如皮肤厚度、雄性生育力和神经加工等特征。除了在单核吞噬细胞及其前体上表达外，CSF-1受体（CSF-1R）在女性生殖道某些非单核吞噬细胞上的表达以及对op/op小鼠的研究表明，CSF-1在女性生殖中起重要作用。将循环CSF-1恢复到op/op小鼠体内已初步确定了通过细胞表面CSF-1的合成或CSF-1蛋白聚糖的隔离而受到体液或局部调节的靶细胞群体。CSF-1R是由c-fms原癌基因产物编码的酪氨酸激酶。几个研究小组利用在成纤维细胞中表达鼠源或人源CSF-1R的细胞，确定了激酶活性的需求以及各种受体酪氨酸磷酸化位点对CSF-1刺激的信号通路的重要性。为了研究巨噬细胞中CSF-1R信号传导后的情况，已经鉴定出了响应CSF-1而在酪氨酸上快速磷酸化的蛋白质，以及与它们相关的蛋白质。本文讨论了对其中几种蛋白质的研究，包括蛋白酪氨酸磷酸酶1C、c-cbl原癌基因产物和蛋白酪氨酸磷酸酶-phi。
