We previously reported the isolation of PR2257, a novel avian sarcoma
retrovirus which transduced the c-src protooncogene. The v-src gene of
PR2257 differs from the c-src gene by a sequence change after amino a
cid 525, resulting in the replacement of tyrosine 527 by a valine, and
an extension of the open reading frame into the non coding region of
c-src. We investigated the respective roles of Tyr527 mutation and of
the C-terminal extension in activating the oncogenic properties of c-s
rc. Therefore we overexpressed the wild type c-src gene and c-src vari
ants, carrying either a substitution of tyrosine 527 or an extension o
f the C-terminus or both modifications in combination, in chicken embr
yo fibroblasts and post mitotic neuroretina (NR) cells, using replicat
ion defective retroviruses. We also used in vivo inoculation of plasmi
d DNA to assess the tumorigenicity of the various c-src genes, We repo
rt that, in contrast to previous results, overexpression of c-src is s
ufficient to induce NR cell division, While mutation of tyrosine 527 a
lone significantly activates c-src transforming and tumorigenic proper
ties, its combination with the C-terminal extension of PR2257 confers
to this gene full oncogenic properties and increased metastatic potent
ial as compared to the v-src of Rous sarcoma virus strains.