Regulation of pp60c-src expression in rat and mouse fibroblasts by an inducible antisense gene: effects on serum regulation of growth and polyoma virus middle T function.
Expression of antisense c-src RNAs in rat and mouse fibroblasts had a dramatic effect on the function of polyoma virus middle T (mT). Antisense c-src RNA decreased the amount of mT:pp60c-src complexes in de novo virus-infected cells and prevented expression of the transformed phenotype in rat F111 cells. Expression of antisense c-src RNA in infected NIH3T3 cells also reduced the formation of mT:pp60c-src complexes but did not affect the ability of polyoma virus to carry out a productive infection. Further analysis of the effects of antisense c-src RNA in uninfected cells revealed that pp60c-src is required for cell growth. When pp60c-src synthesis was reduced, F111 cells stopped proliferating and showed decreased S6 phosphorylation in response to serum. However, F111 cells expressing reduced pp60c-src could be efficiently transformed by v-rasHa, even in the presence of low serum. Thus, pp60c-src appears to function as a component of a signal transduction pathway which regulates cell proliferation in response to serum.
Talmage
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DA
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115.
Riney
C
C
Benjamin
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TL
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology*; D001790:Blood Physiological Phenomena; D002455:Cell Division / Q000502:physiology; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D015151:Immunoblotting; D051379:Mice; D010766:Phosphorylation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000096:biosynthesis* / Q000235:genetics; D016372:RNA, Antisense / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D014779:Virus Replication / Q000235:genetics
D000952:Antigens, Polyomavirus Transforming; D016372:RNA, Antisense; D003907:Dexamethasone; D016392:Proto-Oncogene Proteins pp60(c-src)