Limited redundancy of survival signals from the type 1 insulin-like growth factor receptor

The type 1 insulin-like growth factor receptor (IGF-IR) is effective in protecting cells from a variety of apoptotic injuries. In 32D murine hemopoietic cells, the IGF-IR sends three separate survival signals, through insulin receptor substrate-1, Shc, and mitochondrial Raf translocation. We report here that these three pathways for survival have a limited redundancy. If one of these pathways is blocked, the IGF-IR can still protect 32D cells from apoptosis induced by interleukin-3 withdrawal. However, when two of the three pathways are inactivated, the receptor is no longer capable to protect cells from apoptosis. The survival signal can use any two pathway combinations.