c-Src facilitates tumorigenesis by phosphorylating and activating G6PD.
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| Abstract |
Glucose-6-phosphate dehydrogenase (G6PD) is the first and rate-limiting enzyme in pentose phosphate pathway (PPP), excessive activation of which has been considered to be involved in tumorigenesis. Here, we show that tyrosine kinase c-Src interacts with and phosphorylates G6PD at Tyr 112. This phosphorylation enhances catalytic activity of G6PD by dramatically decreasing its Km value and increasing its Kcat value for substrate glucose-6-phosphate. Activated G6PD therefore augments the PPP flux for NADPH and ribose-5-phosphate production which is required for detoxification of intracellular reactive oxygen species (ROS) and biosynthesis of cancer cells, and eventually contributes to tumorigenesis. Consistently, c-Src activation is closely correlated with tyrosine phosphorylation and activity of G6PD in clinical colorectal cancer samples. We thus uncover another aspect of c-Src in promoting cell proliferation and tumorigenesis, deepening our understanding of c-Src as a proto-oncogene.
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| Authors | Huanhuan Ma, Fengqiong Zhang, Lin Zhou, Tingyan Cao, Dachao Sun, Shixiong Wen, Jinpei Zhu, Zhaoqianyu Xiong, Ming-Tong Tsau, Mei-Ling Cheng, Li-Man Hung, Yanming Zhou, Qinxi Li |
| Journal | Oncogene (Oncogene) Vol. 40 Issue 14 Pg. 2567-2580 (04 2021) ISSN: 1476-5594 [Electronic] England |
| PMID | 33686238 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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