The carboxy-terminal domains of erbB-2 and epidermal growth factor receptor exert different regulatory effects on intrinsic receptor tyrosine kinase function and transforming activity.

摘要: The erbB-2 gene product, gp185erbB-2, displays a potent transforming effect when overexpressed in NIH 3T3 cells. In addition, it possesses constitutively high levels of tyrosine kinase activity the absence exogenously added ligand. this study, we demonstrate that its carboxy-terminal domain exerts an enhancing on and activities. A premature termination mutant protein, lacking entire (erbB-2 delta 1050), showed 40-fold reduction ability lowered vivo for intracellular substrates. When was substituted analogous region epidermal growth factor receptor (EGFR) (EGFR/erbB-2COOH chimera), conferred erbB-2-like properties to EGFR, including factor, elevated constitutive autokinase vitro, phosphorylate phospholipase C-gamma. Conversely, chimeric molecule bearing EGFR (erbB-2/EGFRCOOH chimera) reduced with respect wild-type only slightly more efficient than 1050 mutant. Thus, conclude domains exert different regulatory effects function biological activity. up regulation gp185erbB-2 enzymatic exerted by can explain, at least part, level