Changes in amino-terminal sequences of pp60src lead to decreased membrane association and decreased in vivo tumorigenicity.
We have suggested previously that the amino-terminal 8 kilodaltons of pp60src may serve as a structural hydrophobic domain through which pp60src attaches to plasma membranes. Two isolates of recovered avian sarcoma viruses (rASVs), 1702 and 157, encode pp60src proteins that have alterations in this amino-terminal region. The rASV 1702 src protein (56 kilodaltons) and the 157 src protein (62.5 kilodaltons) show altered membrane association, and fractionate largely as soluble, cytoplasmic proteins in aqueous buffers, ion contrast with the membrane association of more than 80% of the src protein of standard avian sarcoma virus under the identical fractionation procedure. Plasma membranes purified from cells transformed by these rASVs contain less than 10% of the amount of pp60src found in membranes purified from cells transformed by Rous sarcoma virus or control rASVs. The altered membrane association of these src proteins had little or no effect on the properties of chick embryo fibroblasts transformed in monolayer culture. In contrast, rASV 1702 showed reduced in vivo tumorigenicity compared with Rous sarcoma virus or with other rASVs that encode membrane-associated src proteins. Rous sarcoma virus-induced tumors are malignant, poorly differentiated sarcomas that are lethal to their hosts. rASV 1702 induces a benign, differentiated sarcoma that regresses and is not lethal to its hosts. These data support the role of amino-terminal sequences in the membrane association of pp60src, and suggest that the amino terminus of pp60src may have a critical role in the promotion of in vivo tumorigenicity.
D000595:Amino Acid Sequence; D000818:Animals; D001358:Avian Sarcoma Viruses / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002642:Chick Embryo; D003673:Defective Viruses / Q000502:physiology; D005347:Fibroblasts; D015688:Oncogene Protein pp60(v-src); D010770:Phosphotransferases / Q000378:metabolism; D001357:Sarcoma, Avian / Q000209:etiology*; D014764:Viral Proteins / Q000378:metabolism*
D014764:Viral Proteins; D010770:Phosphotransferases; D015688:Oncogene Protein pp60(v-src)