[A study on Fgr expression and its associated molecules in murine lymphoid and haematopoietic tissues]

The c-fgr gene is a member of the src family of proto-oncogene tyrosine kinases. A monoclonal antibody (2H2 mAb) which recognizes the unique N-terminal domain of the murine c-fgr gene product (Fgr) has been established. Immune complex kinase assay with a monocytic leukemia cell line demonstrated that 2H2 precipitated a 59 kilodalton (kDa) protein, which corresponds to the molecular weight of murine Fgr. Fgr was expressed highly in lymph nodes, slightly in spleen and peripheral blood leukocytes and barely in thymus. The Fgr was hardly detectable in bone marrow. Immunohistochemical analysis showed that the expression of Fgr was restricted to cells of monocyte/macrophage lineage located in the marginal zone of the spleen and in the paracortical zone and medulla of lymph nodes. However, various haematopoietic or lymphoid tumor cell lines different from a lineage of monocyte/macrophage were shown to express Fgr molecule by immune complex kinase assay. Although normal resting haematopoietic or lymphoid cells did not express Fgr protein, activated T and B cells expressed Fgr. In the presence of a mild detergent, the Fgr was co-immunoprecipitated with a 75 kDa protein (p75) and several other molecules expressed on the cell surface membrane. Furthermore, the molecule co-immunoprecipitated with Ly6C molecule from a macrophage cell line showed protein tyrosine kinase (PTK) activity. Peptide mapping showed that this kinase activity was derived from Fgr. The similarity of the relationship between this intramembrane p75 and/or Ly6C and the cytoplasmic Fgr to the relationships previously reported between T cell antigen receptor complex including CD4 and CD8 coreceptors, and Lck or Fyn in T cells and between surface IgM and Lyn or Blk in B cells suggested that the Fgr and p75 or Ly6C are indeed associated each other and responsible for recognition of extracellular substances (either cellular or non-cellular) and for signal transduction. It seems likely that these molecules are involved in activation of cells of monocyte/macrophage lineage.