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Sci. STKE, 6 January 2004
Vol. 2004, Issue 214, p. tw4
[DOI: 10.1126/stke.2142004tw4]

EDITORS' CHOICE

GROWTH FACTORS An Arrestin Role at the IGF-1 Receptor

Povsic et al. investigated the role of β-arrestins in the activation of phosphatidylinositol 3-kinase (PI3K) by insulin-like growth factor 1 (IGF-1) and discovered that, unexpectedly, this involved a mechanism independent of the tyrosine kinase activity of the IGF-1 receptor. β-Arrestins are recruited to heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) upon agonist binding and are involved in GPCR desensitization, as well as in activating various signaling pathways, and they are best known for their association with GPCRs. However, β-arrestin1 is also recruited to two related receptor tyrosine kinases--the insulin receptor and the IGF-1 receptor. IGF-1 signaling, which has been implicated in cell differentiation and proliferation, involves the activation of PI3K. Using two mouse embryo fibroblast lines that differed only in β-arrestin1 expression, Povsic et al. showed that IGF-1-mediated activation of PI3Kα; the subsequent recruitment to the plasma membrane, phosphorylation, and activation of Akt; and the inhibition of apoptosis by IGF-1 after serum withdrawal all depended on β-arrestin1. Pharmacologic analysis indicated that activation of PI3K and Akt was independent of IGF-1 receptor tyrosine kinase activity or the phosphorylation of the adaptor protein insulin receptor substrate. PI3K activation was also independent of Src and of IGF-1 activation of Gi (the family of G protein α subunits that can inhibit adenylyl cyclases). Thus, β-arrestins appear to mediate PI3K activation in response to IGF-1 through a novel pathway that is independent of the tyrosine kinase activity of the IGF-1 receptor.

T. J. Povsic, T. A. Kohout, R. J. Lefkowitz, β-Arrestin1 mediates insulin-like growth factor 1 (IGF-1) activation of phosphatidylinositol 3-kinase (PI3K) and anti-apoptosis. J. Biol. Chem. 278, 51334-51339 (2003). [Abstract] [Full Text]

Citation: An Arrestin Role at the IGF-1 Receptor. Sci. STKE 2004, tw4 (2004).


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