Hatakeyama S, Iwabuchi K, Ogasawara K, Good R A, Onoé K
Section of Pathology, Hokkaido University, Sapporo, Japan.
Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3458-62. doi: 10.1073/pnas.91.8.3458.
The c-fgr gene is a member of the Src family of protooncogene tyrosine kinases. A monoclonal antibody (2H2) that recognizes the specific region of the N-terminal domain of the murine c-fgr gene product (Fgr) has been established. With an immune complex kinase assay in a monocytic leukemia cell line, 2H2 monoclonal antibody was shown to precipitate a 59-kDa protein that corresponds in molecular mass to murine Fgr. Fgr was expressed highly in lymph nodes, slightly in spleen and peripheral blood leukocytes, and barely in the thymus and was not detected in bone marrow. In the presence of a mild detergent, Fgr was coimmunoprecipitated with a 70-kDa protein (p70) or with p70 plus several other molecules that were expressed on the cell-surface membrane of macrophage tumor cell lines PU5-1.8 and J774.1, respectively. By contrast, Fgr was not coimmunoprecipitated with a low-affinity receptor for the Fc portion of IgG that is associated with human Fgr. The molecule was also coimmunoprecipitated with the Ly6C molecule from a macrophage cell line (J774.1) that showed protein-tyrosine kinase activity. Peptide mapping revealed that this kinase activity was derived from Fgr. The similarity of relationship between this intramembrane p70 and/or Ly6C and cytoplasmic Fgr to 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, suggests that the Fgr and p70 or Ly6C are, indeed, associated with each other and in the murine system may be responsible for recognition of extracellular substances (either cellular or noncellular) and for signal transduction in cells of monocyte/macrophage lineage.
c-fgr基因是原癌基因酪氨酸激酶Src家族的成员。一种识别鼠源c-fgr基因产物（Fgr）N端结构域特定区域的单克隆抗体（2H2）已被制备。在单核细胞白血病细胞系中通过免疫复合物激酶分析表明，2H2单克隆抗体能沉淀出一种分子量为59 kDa的蛋白质，该蛋白质分子量与鼠源Fgr相对应。Fgr在淋巴结中高表达，在脾脏和外周血白细胞中轻度表达，在胸腺中几乎不表达，在骨髓中未检测到。在温和去污剂存在的情况下，Fgr分别与一种70 kDa的蛋白质（p70）或与p70以及巨噬细胞肿瘤细胞系PU5-1.8和J774.1细胞膜上表达的其他几种分子共免疫沉淀。相比之下，Fgr不与与人源Fgr相关的IgG Fc低亲和力受体共免疫沉淀。该分子也能与来自具有蛋白酪氨酸激酶活性的巨噬细胞系（J774.1）的Ly6C分子共免疫沉淀。肽图谱分析表明这种激酶活性源自Fgr。这种膜内p70和/或Ly6C与胞质Fgr之间的关系与先前报道的T细胞抗原受体复合物（包括CD4和CD8共受体）与T细胞中的Lck或Fyn之间以及B细胞中表面IgM与Lyn或Blk之间的关系相似，这表明Fgr和p70或Ly6C确实相互关联，并且在鼠类系统中可能负责识别细胞外物质（细胞或非细胞）以及单核细胞/巨噬细胞系细胞中的信号转导。
