title: CSF-1 signaling in macrophages: pleiotrophy through phosphotyrosine-based signaling pathways.
abstract: Colony stimulating factor-1 (CSF-1, also known as macrophage-colony stimulating factor, M-CSF) has long been known as the primary growth factor regulating survival, proliferation and differentiation of macrophages and other mononuclear phagocytic (MNP) lineage cells. CSF-1 was subsequently identified as a monocyte/macrophage chemokine, a capacity now recognized to be integral to many of the deleterious as well as positive roles of macrophages in development, homeostasis and disease. The pleiotrophic actions of CSF-1 are all transduced by its high affinity receptor, the CSF-1R, a receptor tyrosine kinase (RTK) and the cellular homologue of the v-fms oncoprotein. While the CSF-1R is the sole receptor for CSF-1, an alternative functional ligand for the receptor, interleukin-34 (IL-34), was recently identified. CSF-1-induced CSF-1R activation triggers autophosphorylation of several intracellular tyrosine residues, leading to initiation of an array of phosphotyrosine-based signaling cascades that mediate the wide variety of cellular responses to CSF-1. Dissecting the contributions of the different phosphorylated tyrosine motifs of the receptor to downstream signaling events in macrophages is not only important for our understanding of CSF-1R function, but also for the development of inhibitors to treat diseases where infiltrating macrophages contribute to their progression. This review will outline our current understanding of the CSF-1/CSF-1R signaling axis and describe how a novel macrophage cell line system, which allows examination of CSF-1R signaling in a mature macrophage context, is helping us to tease apart the diverse signaling pathways initiated by CSF-1R activation.
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Kellie A
authors.initials: KA
authors.lastname: Mouchemore
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Pixley
mesh_terms: D001327:Autoimmune Diseases / Q000473:pathology; D002454:Cell Differentiation; D006801:Humans; D007249:Inflammation / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D009369:Neoplasms / Q000473:pathology; D015398:Signal Transduction
chemical_list: D016173:Macrophage Colony-Stimulating Factor