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.
AffiliationInstitut für Biochemie, OE 4310, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30623 Hannover, Germany.
MetadataShow full item record
AbstractMacrophage 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.
CitationThe 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. 2004, 23 (39):6581-9 Oncogene
- FMIP, a novel Fms-interacting protein, affects granulocyte/macrophage differentiation.
- Authors: Tamura T, Mancini A, Joos H, Koch A, Hakim C, Dumanski J, Weidner KM, Niemann H
- Issue date: 1999 Nov 11
- cAMP inhibits CSF-1-stimulated tyrosine phosphorylation but augments CSF-1R-mediated macrophage differentiation and ERK activation.
- Authors: Wilson NJ, Cross M, Nguyen T, Hamilton JA
- Issue date: 2005 Aug
- The related adhesion focal tyrosine kinase (RAFTK) is tyrosine phosphorylated and participates in colony-stimulating factor-1/macrophage colony-stimulating factor signaling in monocyte-macrophages.
- Authors: Hatch WC, Ganju RK, Hiregowdara D, Avraham S, Groopman JE
- Issue date: 1998 May 15
- A novel 110 kDa form of myosin XVIIIA (MysPDZ) is tyrosine-phosphorylated after colony-stimulating factor-1 receptor signalling.
- Authors: Cross M, Csar XF, Wilson NJ, Manes G, Addona TA, Marks DC, Whitty GA, Ashman K, Hamilton JA
- Issue date: 2004 May 15
- STAP-2 regulates c-Fms/M-CSF receptor signaling in murine macrophage Raw 264.7 cells.
- Authors: Ikeda O, Sekine Y, Kakisaka M, Tsuji S, Muromoto R, Ohbayashi N, Oritani K, Yoshimura A, Matsuda T
- Issue date: 2007 Jul 6