Peptide antibodies to the human c-fyn gene product demonstrate pp59c-fyn is capable of complex formation with the middle-T antigen of polyomavirus.

Abstract

The c‐fyn proto‐oncogene is a member of a family of closely related genes of which c‐src is the prototype. Using peptide antibodies which had been raised against sequences predicted to be specific for the human c‐fyn gene product, the c‐fyn protein was identified. It is a tyrosine kinase with apparent mol. wt of 59 kd that is also phosphorylated and myristylated. Like pp60c‐src and pp62c‐yes, pp59c‐fyn is able to form a stable complex with middle‐T antigen, the transforming protein of polyomavirus. The transformation‐defective middle‐T mutant NG59, which is unable to associate stably with pp60c‐src does not associate with pp59c‐fyn. In contrast to pp60c‐src, complex formation with middle‐T antigen does not lead to a significant increase in the tyrosine kinase activity of pp59c‐fyn. These findings lead us to suggest that middle‐T mediated transformation may be a consequence of the deregulation of several members of the src‐family of protein tyrosine kinases.

Signal transduction in mammary tumorigenesis: a transgenic perspective

“…Infection of newborn or nu/nu mice with PyV frequently results in the induction of mammary tumors (Berebbi et al, 1990), requiring a functional MT antigen to induce tumor formation (Israel et al, 1979). PyV MT antigen lacks intrinsic biochemical activity (Kaplan et al, 1988) but rather exerts its oncogenic e ects through its association with the c-Src PTKs (Cheng et al, 1988;Courtneidge and Smith, 1983;Kornbluth et al, 1986;Kypta et al, 1988) and other signaling molecules such as Shc and PI3'K. Indeed, genetic analysis of MT mutants de®cient in Src, PI3K or Shc interaction are invariably transformation incompetent (Campbell et al, 1994;Charmichel et al, 1984;Dilworth et al, 1994;Druker et al, 1992;Markland et al, 1986;reviewed in Markland and Smith, 1987).…”

Association between src-kinases and the polyoma virus oncogene middle T-antigen requires PP2A and a specific sequence motif

“…It is now clear that MT transforms cells by stimulating many of the pathways used by tyrosine kinase associated growth factor receptors (Dilworth, 1995), and so can be used to study receptor signalling. MT binds the regulatory, A, and catalytic, C, subunits of protein phosphatase 2A (PP2A) (Pallas et al, 1990;Walter et al, 1990), and three members of the srcfamily of tyrosine kinases, pp60 c-src (Courtneidge and Smith, 1983), pp62 c-yes (Kornbluth et al, 1987), and pp59 c-fyn (Cheng et al, 1988;Horak et al, 1989;Kypta et al, 1988). As a consequence, the kinase activity of pp60 c-src , and probably pp62 c-yes , is stimulated (Bolen et al, 1984;Courtneidge, 1985).…”

Polyomavirus middle-sized tumor antigen modulates c-Jun phosphorylation and transcriptional activity.

“…MT is a membrane-associated protein that forms a complex with several cellular proteins potentially involved in growth control, including pp60c-src (2) and other members of the src family (3,4), the 85-kDa and 110-kDa subunits of phosphatidylinositol (PI) 3-kinase (5,6), and the A and C subunits of protein phosphatase 2A (7,8). MT increases the activity of pp60c-src in the complex, at least in part by preventing the phosphorylation of an inhibitory site, Tyr-527 (9,10).…”