• PMID: 25693802
• Gene Name: IGF1R
• Condition: Regulation of sperm capacitation
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Regulation of sperm capacitation

Quantitative phosphoproteomics analysis reveals a key role of insulin growth factor 1 receptor (IGF1R) tyrosine kinase in human sperm capacitation

Wang J, Qi L, Huang S, Zhou T, Guo Y, Wang G, Guo X, Zhou Z, Sha J.

One of the most important changes during sperm capacitation is the enhancement of tyrosine phosphorylation. However, the mechanisms of protein tyrosine phosphorylation during sperm capacitation are not well studied. We used label-free quantitative phosphoproteomics to investigate the overall phosphorylation events during sperm capacitation in humans and identified 231 sites with increased phosphorylation levels. Motif analysis using the NetworKIN algorithm revealed that the activity of tyrosine phosphorylation kinases insulin growth factor 1 receptor (IGF1R)/insulin receptor is significantly enriched among the up-regulated phosphorylation substrates during capacitation. Western blotting further confirmed inhibition of IGF1R with inhibitors GSK1904529A and NVP-AEW541, which inhibited the increase in tyrosine phosphorylation levels during sperm capacitation. Additionally, sperm hyperactivated motility was also inhibited by GSK1904529A and NVP-AEW541 but could be up-regulated by insulin growth factor 1, the ligand of IGF1R. Thus, the IGF1R-mediated tyrosine phosphorylation pathway may play important roles in the regulation of sperm capacitation in humans and could be a target for improvement in sperm functions in infertile men. CI - © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. FAU - Wang, Jing AU - Wang J AD - From the ‡State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China. FAU - Qi, Lin AU - Qi L AD - From the ‡State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China. FAU - Huang, Shaoping AU - Huang S AD - From the ‡State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China. FAU - Zhou, Tao AU - Zhou T AD - From the ‡State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China. FAU - Guo, Yueshuai AU - Guo Y AD - From the ‡State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China. FAU - Wang, Gaigai AU - Wang G AD - From the ‡State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China. FAU - Guo, Xuejiang AU - Guo X AD - From the ‡State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China guo_xuejiang@njmu.edu.cn zhouzm@njmu.edu.cn. FAU - Zhou, Zuomin AU - Zhou Z AD - From the ‡State Key Laboratory of Reproductive Medicine, Collaborative Innovation Center of Genetics and Development, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China guo_xuejiang@njmu.edu.cn zhouzm@njmu.edu.cn.