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

The production, survival and function of monocytes and macrophages are regu lated by the macrophage colony-stimulating factor (M-CSF or CSF-1) through its tyrosine kinase receptor Fms, Binding of M-CSF results in Fms autophosp horylation on specific tyrosines that act as docking sites for intracellula r signaling molecules containing SH2 domains. Using a yeast two-hybrid scre en, 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 Gr b2 adaptor. Accordingly, Mona interacts with activated Fms on phosphorylate d Tyr697, which is also the Grb2-binding site. Furthermore, Mona contains a unique proline-rich region located between the SH2 domain and the C-termin al SH3 domain, and is apparently devoid of any catalytic domain. Mona expre ssion is restricted to two hematopoietic tissues: the spleen and the periph eral blood mononuclear cells, and is induced rapidly during monocytic diffe rentiation of the myeloid NFS-60 cell line in response to M-CSF. Strikingly , overexpression of Mona in bone marrow cells results in strong reduction o f M-CSF-dependent macrophage production in vitro. Taken together, our resul ts suggest an important role for Mona in the regulation of monocyte/macroph age development as controlled by M-CSF.