Transmembrane signaling by epidermal growth factor receptors lacking autophosphorylation sites

摘要: Mutant epidermal growth factor (EGF) receptors in which the five known tyrosine autophosphorylation sites (tyrosines 992, 1068, 1086, 1148, and 1173) were replaced with phenylalanine residues expressed NIH-3T3 cells (5F-EGFR) transmembrane signaling parameters compared expressing wild-type EGF receptor (WT-EGFR). clones chosen similar numbers of Scatchard analysis 125I-EGF binding showed high low affinity equal affinities for both types. stimulated phosphorylation proteins to a much lesser degree 5F-EGFR relative WT-EGFR. Tyrosine was 2-4% Surprisingly, WT-EGFR or little difference dose response EGF-stimulated [3H]thymidine incorporation stimulation mitogen-activated protein kinase activity. However, did not induce anchorage-independent same extent as it treatment failed elicit an increase phosphatidylinositol 3-kinase activity stimulate hydrolysis phosphoinositides phospholipase C-gamma 1. These data suggest that significant proportion can occur through altered capacity interact src homology 2 domain-containing proteins.