Insulin-like growth factor-I receptor (IGF-IR) is an RTK that stimulates growth in many different cell types, blocks apoptosis, acts as an intermediate of many growth hormone responses and may stimulate the growth of some types of cancer. The IGF-IR cognate ligand insulin-like growth factor-I (IGF-I) promotes association of IGF-IR with Shc, GRB2 and Sos 1, which initiates Ras and ERK kinase cascades, thereby modifying transcription factor activity, such as activation of the Elk transcription factors. The modular phosphotyrosine binding (PTB) domains of insulin receptor substrate (IRS)-1 and -2 can associate with active IGF-IR and initiate phosphatidylinositol 3-kinase-dependent downstream signals.