Origin and functional properties of the major gene product of the Snyder-Theilen strain of feline sarcoma virus.

Abstract

The only known product of the Snyder-Theilen strain of feline sarcoma virus (ST-FeSV) is a 85,000-dalton protein, designated ST P85, that contains feline leukemia virus gag gene encoded proteins (p15, p12, and a fragment of p30) and a sarcoma virus-specific polypeptide. Antibodies directed against the latter immunoprecipitated a 92,000-dalton phosphoprotein (NCP 92) expressed at low levels in normal feline embryo fibroblasts as well as in feline cells of epithelial or lymphoid origin. Normal cellular proteins crossreactive with ST P85 were also detected in cell lines from various other mammalian species. These results suggest that the ST-FeSV sequences encoding for the sarcoma virus-specific domain of ST P85 originated from an evolutionarily conserved cellular gene expressed in cells of independent differentiation lineage. Immunoprecipitates containing ST-FeSV P85 exhibited a protein kinase activity that specifically phosphorylated tyrosine residues. The physiological significance of this finding is illustrated by the finding that phosphotyrosine is an intrinsic component of ST

P85 gag-mos encoded by ts110 Moloney murine sarcoma virus has an associated protein kinase activity

“…This protein kinase activity, usually detected as autophosphorylation, has been found to be associated with transforming proteins of Rous sarcoma virus (10,11), Abelson murine leukemia virus (MuLV) (12), Snyder-Theilen strain offeline sarcoma virus (13,14), Y73 avian sarcoma virus (15), and Fuginami avian sarcoma virus (16). First identified in the Rous sarcoma virus (10), the protein kinase activity ofphosphorylated p6{src has been shown to be an intrinsic property of the transforming protein (17,18).…”

Biosynthesis and glycosylation of the epidermal growth factor receptor in human tumor-derived cell lines A431 and Hep 3B.

“…Whether cleavage of the C terminus of the EGF receptor by an apparently ubiquitous Ca2+-dependent protease has some function, for example that of generating a second messenger, in relaying the mitogenic signal remains an intriguing if unresolved question (19,58). The EGF receptor is also a tyrosine-specific protein kinase (53), as are at least three other hormone receptors (15,26,45) and several of the transforming proteins encoded by RNA tumor viruses of the Rous sarcoma gene family (2,4,10,24,32,41,44,54,57). This suggests that phosphorylation of tyrosine may underlie a more general mechanism of growth control.…”

Treatment for chronic myelogenous leukemia: the long road to imatinib

“…Moreover, v-Src activity was found to lead to a large increase in the level of phosphotyrosine in cellular proteins that is essential for malignant transformation (30). Within a year, three other distinct retroviral oncoproteins had been reported to have tyrosine kinase activity (18,31,32), and the EGF receptor had also been shown to have EGF-induced tyrosine kinase activity (33), providing the first concrete link between oncogenesis and growth control and, more importantly, setting the stage for the subsequent development of tyrosine kinase inhibitors as cancer drugs.…”