Epidermal Growth Factor-induced Rapid Retinoblastoma Phosphorylation at Ser780 and Ser795 Is Mediated by ERK1/2 in Small Intestine Epithelial Cells

摘要: The retinoblastoma protein Rb is critical for the regulation of mammalian cell cycle entry. Hypophosphorylated considered to be active form and directs G1 arrest, while hyperphosphorylated permits transition from S phase proliferation. Upon stimulation by various growth factors, appears phosphorylated a cascade phosphorylation events mediated mainly kinases associated with cyclins D E. Here we report that in prototype small intestine crypt stem cells (RIEC-6), either epidermal factor or fetal bovine serum results an unexpected rapid sustained at sites Ser780, Ser795, Thr821 which precedes cyclin D1 expression, D1/cdk4 complex formation, cdk4 kinase activity. Ser780 Ser795 prevented MEK, but not phosphatidylinositol 3-kinase, inhibitors. In vitro, directly ERK1/2 as shown [γ-32P]ATP labeling. are further directed assays using recombined immunoprecipitated phospho-ERK1/2 mitogen stimulated cells. Pull-down revealed interacts their inactive unphosphorylated forms. EGF stimulation, co-immunoprecipitates together Rb. Collectively, these demonstrate novel specific induced epithelial intestine. These data specifically identify responsible targeted Ser795. It could important link between mitogenic signal Rb, thereby providing response mechanism machinery.