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β-Arrestin1 Mediates Insulin-like Growth Factor 1 (IGF-1) Activation of Phosphatidylinositol 3-Kinase (PI3K) and Anti-apoptosis
Open accessAbstract
beta-arrestins (1 and 2) are widely expressed cytosolic proteins that play central roles in G protein-coupled receptor signaling. beta-arrestin1 is also recruited to the insulin-like growth factor 1 (IGF-1) receptor, a receptor tyrosine kinase, upon agonist binding. Here we report that, in response to IGF-1 stimulation, beta-arrestin1 mediates activation of phosphatidylinositol 3-kinase in a pathway that leads to the subsequent activation of Akt and anti-apoptosis. This process is independent of both Gi and ERK activity. The pathway fails in mouse embryo fibroblasts lacking both beta-arrestins and is restored by stable transfection of beta-arrestin1. Remarkably, this pathway is insensitive to chemical inhibition of IGF-1 receptor tyrosine kinase activity. These results suggest that, in addition to their roles in G protein-coupled receptor signaling, beta-arrestins couple the IGF-1 receptor tyrosine kinase to the phosphatidylinositol 3-kinase system and suggest that this mechanism is operative independently of the tyrosine kinase activity of the receptor.
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Cites
Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling
SHEPHERD, P. R., WITHERS, D. J., & SIDDLE, K. (1998) · Biochemical Journal · doi:10.1042/bj3330471 · Cited by 953
Martin, T. F. J. (1998) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.14.1.231 · Cited by 522
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Self-citationHistorical review: A brief history and personal retrospective of seven-transmembrane receptors
Lefkowitz, R. J. (2004) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2004.06.006 · Cited by 417
Self-citationRole and regulation of autophagy in cancer
Chen, N., & Karantza-Wadsworth, V. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2008.12.013 · Cited by 357
New Roles for β-Arrestins in Cell Signaling: Not Just for Seven-Transmembrane Receptors
Lefkowitz, R. J., Rajagopal, K., & Whalen, E. J. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.11.007 · Cited by 301
Self-citationRubovitch, V., Edut, S., Sarfstein, R., Werner, H., & Pick, C. G. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.01.021 · Cited by 61
Metadata
- Authors
- Povsic, T. J., Kohout, T. A., & Lefkowitz, R. J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-12
- Volume
- 278
- Issue
- 51
- Pages
- 51334-51339
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2005351906
- Cited by
- 174
- References
- 2
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Povsic, T. J., Kohout, T. A., & Lefkowitz, R. J. (2003). β-Arrestin1 Mediates Insulin-like Growth Factor 1 (IGF-1) Activation of Phosphatidylinositol 3-Kinase (PI3K) and Anti-apoptosis. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m309968200
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