Heregulin-dependent translocation and hyperphosphorylation of ErbB-2

Previous data have shown that in several tumor cells lines the addition of heregulin results in the translocation of ErbB-4 to a detergent-insoluble m embrane fraction where it is hypertyrosine phosphorylated, The data herein demonstrate that heregulin or betacellulin, but not EGF, promotes the rapid translocation of ErbB-2, the heterodimerization partner for ErbB-4, to the same detergent-insoluble fraction in T47 D mammary carcinoma cells. The tr anslocation of ErbB-2 and ErbB-4, but not ErbB-3, to this detergent-insolub le fraction is readily detected 2 min after the addition of heregulin, ErbB -2 present in this detergent-insoluble membrane fraction is tyrosine phosph orylated to a level fourfold greater than the majority of cellular ErbB-2 p resent in the detergent-soluble membrane fraction. These results suggest th e ligand-dependent formation of hyperphosphorylated ErbB-4/ErbB-2 dimers co ordinate with translocation to a putative membrane microdomain,