Deregulation of tyrosine kinases in a rat macrophage tumor-ectopic expression of lck

Abstract

AK-5, a spontaneous rat macrophage tumor has 2-3 fold higher membrane-associated tyrosine kinase (TK) activity than normal peritoneal macrophages. lck, the lymphoid-specific TK, is expressed ectopically in AK-5. p56(lck), the protein product of lck, was detected in AK-5 by immunoprecipitation. The surface proteins CD4 and CD8 to which p56(lck) is complexed in lymphocytes are not present an the surface of AK-5. The transcripts of hck, a gene expressed predominantly in myeloid cells are markedly reduced in AK-5. The genomic organization of lck is unaltered. Although the total phosphotyrosine content of proteins is not altered significantly, there is a qualitative change in the profile of phosphotyrosine containing proteins. These results provide evidence for the ectopic expression of lck in a hematopoietic tumor and bolster the existing data implicating the participation of src family TKs in spontaneous neoplasms.