CSF-1 signal transduction.
Colony-stimulating factor-1 (CSF-1) or macrophage-CSF (M-CSF) is a growth factor involved in the proliferation, differentiation, and activation of cells of the monocyte/macrophage lineage. Its receptor is the homodimeric, tyrosine kinase product of the c-fms proto-oncogene, which contains a so-called kinase insert domain. This review focuses mainly on recent studies of signal transduction events that are initiated on interaction of CSF-1 and its receptor. A summary is given of the tyrosine autophosphorylation sites on c-Fms identified to date, including their interaction with various substrates and their possible significance for signal transduction and cellular function. In addition, the signal transduction pathways that have been identified to lie downstream of activated c-Fms are reviewed. Although it is apparent that there have been many recent significant developments in our understanding of CSF-1 signaling, a number of examples are mentioned of significant discrepancies in the literature, some possible reasons for which can sometimes be offered. It is also apparent that any particular biochemical response or signal transduction pathway, even though widespread in other ligand receptor/cellular systems, including those with similar receptor structures to c-Fms, may not be relevant to CSF-1 signaling. The relevance of any potentially important molecular signaling pathway activated by CSF-1 in cells in vitro will ultimately have to be related to the functions of monocytes/macrophages in vivo.
Hamilton
J A
JA
University of Melbourne Department of Medicine, Royal Melbourne Hospital, Parkville, Australia.
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D018797:Cell Cycle Proteins; D000242:Cyclic AMP / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D004705:Endocytosis; D051380:GRB2 Adaptor Protein; D019204:GTP-Binding Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D053613:Janus Kinase 1; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010740:Phospholipases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl; D051567:Proto-Oncogene Proteins c-vav; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000502:physiology*; D019893:Ribosomal Protein S6 Kinases; D050794:STAT1 Transcription Factor; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D015534:Trans-Activators / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018797:Cell Cycle Proteins; D000242:Cyclic AMP; D004268:DNA-Binding Proteins; D051380:GRB2 Adaptor Protein; D019204:GTP-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D053613:Janus Kinase 1; D016173:Macrophage Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010740:Phospholipases; D010744:Phosphoric Monoester Hydrolases; D017853:Phosphotransferases (Alcohol Group Acceptor); D019000:Phosphotyrosine; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D011505:Protein-Tyrosine Kinases; D011506:Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D050721:Proto-Oncogene Proteins c-cbl; D051567:Proto-Oncogene Proteins c-vav; D016283:Proto-Oncogene Proteins p21(ras); D016186:Receptor, Macrophage Colony-Stimulating Factor; D019893:Ribosomal Protein S6 Kinases; D050794:STAT1 Transcription Factor; D055765:Shc Signaling Adaptor Proteins; D017923:Sodium-Hydrogen Exchangers; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D015534:Trans-Activators; D044767:Ubiquitin-Protein Ligases; C495949:Grb2 protein, mouse; C000715470:MAS1 protein, human; C528034:Shc1 protein, mouse; C494080:Stat1 protein, mouse; C496619:Vav1 protein, mouse; C507904:JAK1 protein, human; C507905:Jak1 protein, mouse; C509249:PTPN6 protein, human; C509248:Ptpn6 protein, mouse; C098706:INPPL1 protein, human; C067419:CBL protein, human; C493849:Cbl protein, mouse