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Limited Redundancy of Survival Signals from the Type 1 Insulin-Like Growth Factor Receptor¹

Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Address all correspondence and requests for reprints to: Dr. Renato Baserga, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Room 624 BLSB, Philadelphia, Pennsylvania 19107. E-mail: r_baserga{at}lac.jci.tju.edu

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.

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