Expression of human tyrosine kinase-negative epidermal growth factor receptor amplifies signaling through endogenous murine epidermal growth factor receptor

摘要: Recent findings have suggested that certain ligand-dependent responses to EGF may be propagated in a manner is not dependent on the intrinsic tyrosine kinase activity of epidermal growth factor receptor (EGF-R, Campos-Gonzalez, R., and Glenney, J. Jr. (1992) Biol. Chem. 267, 14535-14538) or, alternatively, these occur through interaction human kinase-deficient EGF-R with an as yet unidentified (Selva, E., Raden, D. L., Davis, R. (1993) 268, 2250-2254). These conclusions represent significant departure from our current understanding signal transduction by kinases. Therefore we examined effect expression kinase-negative murine NIH-3T3-2.2 cells EGF-dependent phosphorylation mitogen-activated protein (MAP-2) kinase. In parental (NIH-3T3-2.2) express low levels endogenous EGF-R, there was no demonstrable coupling MAP-2 transfected unexpected Analysis revealed EGF-R. A level present were also phosphorylated residues displayed autokinase activity. Similar results obtained using unrelated cell line (B82L cells), which previously attributed propagation (Campos-Gonzalez, 14535-14538). Taken together, suggest are able amplify response activation thus leading expressing