Mona, a novel hematopoietic-specific adaptor interacting with the macrophage colony-stimulating factor receptor, is implicated in monocyte/macrophage development.
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.
Bourette
R P
RP
Centre de Génétique Moléculaire et Cellulaire, UMR CNRS 5534, 43 Boulevard du 11 novembre 1918, 69622 Villeurbanne Cedex, France.
Arnaud
S
S
Myles
G M
GM
Blanchet
J P
JP
Rohrschneider
L R
LR
Mouchiroud
G
G
D048868:Adaptor Proteins, Signal Transducing; D000581:Amidohydrolases; D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology*; D011485:Protein Binding; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D014018:Tissue Distribution; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C498726:Mona protein, mouse; D011994:Recombinant Proteins; D016186:Receptor, Macrophage Colony-Stimulating Factor; D000626:Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase