Inhibition of the tyrosine kinase activity of v-src, v-fgr, and v-yes gene products by a monoclonal antibody which binds both amino and carboxy peptide fragments of pp60 super(v-src)

A monoclonal antibody, R2D2, raised to the src gene product of Rous sarcoma virus was found to inhibit the tyrosine protein kinase activity of pp60 super(v-src) in autophosphorylation reactions and in reactions involving exogenously added substrates, such as casein and histone. R2D2 also inhibited the enzymatic activity of two related viral transforming proteins, pp70 super(gag-fgr) and pp90 super(gag-yes). The localization of the R2D2 epitope to the amino- as well as to the carboxy-terminal portions of pp60 super(v-src), together with results of studies analyzing the relative binding efficiencies of R2D2 to the intact protein and to V-8 proteolytic fragments of pp60 super(v-src), are consistent with the view that the R2D2 epitope is conformational in nature and that it is assembled from residues contained within both N-terminal and C-terminal regions of the molecule.