Compartmentalization of SHC, GRB2 and mSOS, and hyperphosphorylation of Raf-1 by EGF but not insulin in liver parenchyma.

摘要: Abstract Rat liver parenchyma harbors equal numbers of epidermal growth factor (EGF) and insulin receptors. Following administration a saturating dose EGF (10 micrograms/100 g body weight), there was rapid (t1/2 approximately 1.1 min) internalization receptor coincident with its tyrosine phosphorylation at residue 1173 recruitment the adaptor protein SHC, association GRB2 Ras guanine nucleotide exchange factor, mSOS, largely in endosomes. This led to cytosolic pool complex tyrosine-phosphorylated mSOS. It demonstrated that these constituents were linked activation by characteristic decrease Raf-1 mobility on SDS-PAGE, which maintained for 60 min after single bolus administered EGF. While (15 weight) beta-subunit internalization, little detectable GRB2, mSOS or any change Raf-1. Therefore, normal physiological target cells vivo, distinct signaling pathways are realized activation, regulation this specificity most probably occurring locus endosome.