Hepatocyte growth factor regulated tyrosine kinase substrate ( HRS ) interacts with PELP 1 and activates MAPK . ^^^ Hepatocyte growth factor regulated tyrosine kinase substrate ( HRS ) interacts with PELP 1 and activates MAPK . ^^^ By using a yeast two hybrid screen , we identified HRS as a novel PELP 1 binding protein providing evidence of a physiologic interaction between HRS and PELP 1 . ^^^ The noted HRS PELP 1 interaction was accompanied by inhibition of the basal coactivator function of PELP 1 upon estrogen receptor transactivation . ^^^ HRS was found to sequester PELP 1 in the cytoplasm , leading to the activation of MAPK in a manner that is dependent on the epidermal growth factor receptor but independent of the estrogen receptor , Shc , and Src . ^^^ |