SP600125 Induces Src and Type I IGF Receptor Phosphorylation Independent of JNK
1
State Key Laboratory of Biotherapy, Section of Oncogene, West China Hospital, Sichuan University, Chengdu 610041, China
2
Laboratory of Stem Cell Biology, West China Hospital, Sichuan University, Chengdu 610041, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2014, 15(9), 16246-16256; https://doi.org/10.3390/ijms150916246
Received: 15 July 2014
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Revised: 27 August 2014
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Accepted: 1 September 2014
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Published: 15 September 2014
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells 2014)
c-Jun N-terminal kinases (JNK) are members of the mitogen-activated protein kinase (MAPK) family that have important roles in signal transduction. The small molecule SP600125 is widely used in biochemical studies as a JNK inhibitor. However, recent studies indicate that SP600125 may also act independent of JNK. Here, we report that SP600125 can induce Src, type I insulin-like growth factor receptor (IGF-IR), Akt and Erk1/2 phosphorylation. Notably, these effects are independent of its inhibition of JNK. Inhibition of Src abrogates the stimulation of IGF-IR, Akt and Erk1/2 phosphorylation. IGF-IR knockdown blunts the induction of both Akt and Erk1/2 phosphorylation by SP600125. Moreover, combination of SP600125 and the Src inhibitor saracatinib synergistically inhibits cell proliferation. We conclude that SP600125 can activate Src-IGF-IR-Akt/Erk1/2 signaling pathways independent of JNK.
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MDPI and ACS Style
Kong, Q.; Hua, H.; Cui, A.; Shao, T.; Song, P.; Jiang, Y. SP600125 Induces Src and Type I IGF Receptor Phosphorylation Independent of JNK. Int. J. Mol. Sci. 2014, 15, 16246-16256. https://doi.org/10.3390/ijms150916246
AMA Style
Kong Q, Hua H, Cui A, Shao T, Song P, Jiang Y. SP600125 Induces Src and Type I IGF Receptor Phosphorylation Independent of JNK. International Journal of Molecular Sciences. 2014; 15(9):16246-16256. https://doi.org/10.3390/ijms150916246
Chicago/Turabian StyleKong, Qingbin, Hui Hua, Anguo Cui, Ting Shao, Peiying Song, and Yangfu Jiang. 2014. "SP600125 Induces Src and Type I IGF Receptor Phosphorylation Independent of JNK" International Journal of Molecular Sciences 15, no. 9: 16246-16256. https://doi.org/10.3390/ijms150916246
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