This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Navarro, M. Articles by Baserga, R. Search for Related Content PubMed PubMed Citation Articles by Navarro, M. Articles by Baserga, R.

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.

This article has been cited by other articles:

				R. S. Douglas, A. G. Gianoukakis, S. Kamat, and T. J. Smith Aberrant Expression of the Insulin-Like Growth Factor-1 Receptor by T Cells from Patients with Graves' Disease May Carry Functional Consequences for Disease Pathogenesis J. Immunol., March 1, 2007; 178(5): 3281 - 3287. [Abstract] [Full Text] [PDF]

				A. Aiello, G. Pandini, F. Frasca, E. Conte, A. Murabito, A. Sacco, M. Genua, R. Vigneri, and A. Belfiore Peroxisomal Proliferator-Activated Receptor-{gamma} Agonists Induce Partial Reversion of Epithelial-Mesenchymal Transition in Anaplastic Thyroid Cancer Cells Endocrinology, September 1, 2006; 147(9): 4463 - 4475. [Abstract] [Full Text] [PDF]

				T. Stromberg, S. Ekman, L. Girnita, L. Y. Dimberg, O. Larsson, M. Axelson, J. Lennartsson, U. Hellman, K. Carlson, A. Osterborg, et al. IGF-1 receptor tyrosine kinase inhibition by the cyclolignan PPP induces G2/M-phase accumulation and apoptosis in multiple myeloma cells Blood, January 15, 2006; 107(2): 669 - 678. [Abstract] [Full Text] [PDF]

				A. Kuribayashi, K. Kataoka, T. Kurabayashi, and M. Miura Evidence that Basal Activity, But Not Transactivation, of the Epidermal Growth Factor Receptor Tyrosine Kinase Is Required for Insulin-like Growth Factor I-Induced Activation of Extracellular Signal-Regulated Kinase in Oral Carcinoma Cells Endocrinology, November 1, 2004; 145(11): 4976 - 4984. [Abstract] [Full Text] [PDF]

				A. R. Uzgare and J. T. Isaacs Enhanced Redundancy in Akt and Mitogen-activated Protein Kinase-induced Survival of Malignant versus Normal Prostate Epithelial Cells Cancer Res., September 1, 2004; 64(17): 6190 - 6199. [Abstract] [Full Text] [PDF]

				M. Prisco, A. Maiorana, C. Guerzoni, G. Calin, B. Calabretta, R. Voit, I. Grummt, and R. Baserga Role of Pescadillo and Upstream Binding Factor in the Proliferation and Differentiation of Murine Myeloid Cells Mol. Cell. Biol., June 15, 2004; 24(12): 5421 - 5433. [Abstract] [Full Text] [PDF]

				K. A. Green, M. J. Naylor, E. T. Lowe, P. Wang, E. Marshman, and C. H. Streuli Caspase-mediated Cleavage of Insulin Receptor Substrate J. Biol. Chem., June 11, 2004; 279(24): 25149 - 25156. [Abstract] [Full Text] [PDF]

				A. Girnita, L. Girnita, F. d. Prete, A. Bartolazzi, O. Larsson, and M. Axelson Cyclolignans as Inhibitors of the Insulin-Like Growth Factor-1 Receptor and Malignant Cell Growth Cancer Res., January 1, 2004; 64(1): 236 - 242. [Abstract] [Full Text] [PDF]

				A. Hongo, H. Kuramoto, Y. Nakamura, K. Hasegawa, K. Nakamura, J. Kodama, and Y. Hiramatsu Antitumor Effects of a Soluble Insulin-Like Growth Factor I Receptor in Human Ovarian Cancer Cells: Advantage of Recombinant Protein Administration in Vivo Cancer Res., November 15, 2003; 63(22): 7834 - 7839. [Abstract] [Full Text] [PDF]

				E. K. Maloney, J. L. McLaughlin, N. E. Dagdigian, L. M. Garrett, K. M. Connors, X.-M. Zhou, W. A. Blattler, T. Chittenden, and R. Singh An Anti-Insulin-like Growth Factor I Receptor Antibody That Is a Potent Inhibitor of Cancer Cell Proliferation Cancer Res., August 15, 2003; 63(16): 5073 - 5083. [Abstract] [Full Text] [PDF]

				L. Sciacca, M. Prisco, A. Wu, A. Belfiore, R. Vigneri, and R. Baserga Signaling Differences from the A and B Isoforms of the Insulin Receptor (IR) in 32D Cells in the Presence or Absence of IR Substrate-1 Endocrinology, June 1, 2003; 144(6): 2650 - 2658. [Abstract] [Full Text] [PDF]

				H. Sun, X. Tu, M. Prisco, A. Wu, I. Casiburi, and R. Baserga Insulin-Like Growth Factor I Receptor Signaling and Nuclear Translocation of Insulin Receptor Substrates 1 and 2 Mol. Endocrinol., March 1, 2003; 17(3): 472 - 486. [Abstract] [Full Text] [PDF]

				D. Yu, H. Watanabe, H. Shibuya, and M. Miura Redundancy of Radioresistant Signaling Pathways Originating from Insulin-like Growth Factor I Receptor J. Biol. Chem., February 21, 2003; 278(9): 6702 - 6709. [Abstract] [Full Text] [PDF]

				G. Bompard, C. Puech, C. Prebois, F. Vignon, and G. Freiss Protein-tyrosine Phosphatase PTPL1/FAP-1 Triggers Apoptosis in Human Breast Cancer Cells J. Biol. Chem., November 27, 2002; 277(49): 47861 - 47869. [Abstract] [Full Text] [PDF]

				M. Prisco, F. Santini, R. Baffa, M. Liu, R. Drakas, A. Wu, and R. Baserga Nuclear Translocation of Insulin Receptor Substrate-1 by the Simian Virus 40 T Antigen and the Activated Type 1 Insulin-like Growth Factor Receptor J. Biol. Chem., August 23, 2002; 277(35): 32078 - 32085. [Abstract] [Full Text] [PDF]

				M. Navarro, B. Valentinis, B. Belletti, G. Romano, K. Reiss, and R. Baserga Regulation of Id2 Gene Expression by the Type 1 IGF Receptor and the Insulin Receptor Substrate-1 Endocrinology, December 1, 2001; 142(12): 5149 - 5157. [Abstract] [Full Text] [PDF]

				M. Prisco, F. Peruzzi, B. Belletti, and R. Baserga Regulation of Id Gene Expression by Type I Insulin-Like Growth Factor: Roles of STAT3 and the Tyrosine 950 Residue of the Receptor Mol. Cell. Biol., August 15, 2001; 21(16): 5447 - 5458. [Abstract] [Full Text] [PDF]

				B Valentinis and R Baserga IGF-I receptor signalling in transformation and differentiation Mol. Pathol., June 1, 2001; 54(3): 133 - 137. [Abstract] [Full Text]

				F. Peruzzi, M. Prisco, A. Morrione, B. Valentinis, and R. Baserga Anti-apoptotic Signaling of the Insulin-like Growth Factor-I Receptor through Mitochondrial Translocation of c-Raf and Nedd4 J. Biol. Chem., July 6, 2001; 276(28): 25990 - 25996. [Abstract] [Full Text] [PDF]