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PMID: 9857184 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Mona, a novel hematopoietic-specific adaptor interacting with the macrophage colony-stimulating factor receptor, is implicated in monocyte/macrophage development.

The EMBO journal ·Vol. 17 ·No. 24 ·1998-12-15 ·Pages 7273-81

Bourette RP, Arnaud S, Myles GM, Blanchet JP, Rohrschneider LR, Mouchiroud G

Abstract

The production, survival and function of monocytes and macrophages are regulated by the macrophage colony-stimulating factor (M-CSF or CSF-1) through its tyrosine kinase receptor Fms. Binding of M-CSF results in Fms autophosphorylation on specific tyrosines that act as docking sites for intracellular signaling molecules containing SH2 domains. Using a yeast two-hybrid screen, we cloned a novel adaptor protein which we called 'Mona' for monocytic adaptor. Mona contains one SH2 domain and two SH3 domains related to the Grb2 adaptor. Accordingly, Mona interacts with activated Fms on phosphorylated Tyr697, which is also the Grb2-binding site. Furthermore, Mona contains a unique proline-rich region located between the SH2 domain and the C-terminal SH3 domain, and is apparently devoid of any catalytic domain. Mona expression is restricted to two hematopoietic tissues: the spleen and the peripheral blood mononuclear cells, and is induced rapidly during monocytic differentiation of the myeloid NFS-60 cell line in response to M-CSF. Strikingly, overexpression of Mona in bone marrow cells results in strong reduction of M-CSF-dependent macrophage production in vitro. Taken together, our results suggest an important role for Mona in the regulation of monocyte/macrophage development as controlled by M-CSF.

MeSH Terms
Adaptor Proteins, Signal Transducing Amidohydrolases Amino Acid Sequence Aminopeptidases/metabolism Animals Bone Marrow Cells/cytology Carrier Proteins/genetics,metabolism Cell Differentiation Gene Expression Regulation Hematopoietic Stem Cells/cytology Leukocytes, Mononuclear/cytology Macrophages/cytology Mice Molecular Sequence Data Monocytes/cytology Protein Binding Receptor, Macrophage Colony-Stimulating Factor/metabolism Recombinant Proteins/metabolism Sequence Homology, Amino Acid Signal Transduction Spleen/cytology Tissue Distribution src Homology Domains
Chemicals
Adaptor Proteins, Signal Transducing Carrier Proteins Mona protein, mouse Recombinant Proteins Receptor, Macrophage Colony-Stimulating Factor Aminopeptidases Amidohydrolases peptide deformylase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Bourette R P
Centre de Génétique Moléculaire et Cellulaire, UMR CNRS 5534, 43 Boulevard du 11 novembre 1918, 69622 Villeurbanne Cedex, France.
Arnaud S
Myles G M
Blanchet J P
Rohrschneider L R
Mouchiroud G
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/17.24.7273
Published
1998-12-15
Pages
7273-81
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1171073
Subset
IM
Databases
GENBANK
AF055465
External Links
PubMed source DOI: 10.1093/emboj/17.24.7273 PMC Full Text View journal details
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