PMID:15221008

Citation	Mancini, A, Koch, A, Whetton, AD and Tamura, T (2004) The M-CSF receptor substrate and interacting protein FMIP is governed in its subcellular localization by protein kinase C-mediated phosphorylation, and thereby potentiates M-CSF-mediated differentiation. Oncogene 23:6581-9
Abstract	Macrophage colony-stimulating factor (M-CSF or CSF-1) and its cognate receptor, the tyrosine kinase c-fms, are essential for monocyte and macrophage development. We have recently identified an Fms-interacting protein (FMIP) that binds transiently to the cytoplasmic domain of activated Fms molecules and is phosphorylated on tyrosine by Fms tyrosine kinase. FMIP is a substrate not only for Fms but also for protein kinase C (PKC). Mutagenesis reveals that this occurs on serines 5 and 6. Adjacent to these sites is a nuclear localization signal (NLS). We show that this NLS is essential for the predominantly nuclear localization of FMIP. Generation of phosphomimetic substitutions on serine residues 5 and 6 confirms that PKC-mediated phosphorylation on this site leads to translocation of FMIP to the cytosol. Furthermore, the mutant FMIP (FMIPSS5,6AA) was detected abundantly in the nucleus even in the presence of activated PKCalpha. Wild-type FMIP and FMIPSS5,6AA inhibited M-CSF-mediated survival signaling, while FMIPSS5,6EE-expressing cells survived and differentiated into macrophages more efficiently than wild-type cells in the presence of M-CSF or TPA. We conclude M-CSF-mediated activation of PKCalpha can potentiate FMIP action to initiate survival/differentiation signaling.
Links	PubMed Online version:10.1038/sj.onc.1207841
Keywords	Animals; Carrier Proteins/metabolism; Cell Differentiation; Enzyme Activation; In Situ Nick-End Labeling; Intracellular Signaling Peptides and Proteins; Macrophage Colony-Stimulating Factor/physiology; Mice; NIH 3T3 Cells; Phosphorylation; Protein Kinase C/metabolism; Receptor, Macrophage Colony-Stimulating Factor/metabolism; Subcellular Fractions/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:THOC5		GO:0005634: nucleus	ECO:0000315:		C		Figure 2	complete CACAO 9013
MOUSE:THOC5	part_of	GO:0005634: nucleus	ECO:0000315: mutant phenotype evidence used in manual assertion		C		Seeded From UniProt	complete

References

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