Attenuation of fibroblast growth factor signaling by poly-N-acetyllactosamine type glycans |
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| Authors: | Kazuhiro Sugihara Toshiaki K Shibata Kayoko Takata Takako Kimura Naohiro Kanayama Roy Williams Shingo Hatakeyama Tomoya O Akama Chu-Wei Kuo Kay-Hooi Khoo Michiko N Fukuda |
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| Institution: | 1. Department of Gynecology and Obstetrics, Hamamatsu University School of Medicine, Hamamatsu City, Shizuoka, Japan;2. Tumor Microenvironment Program, Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA;3. Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan;4. Department of Pharmacology, Kansai University School of Medicine, Osaka, Japan;5. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan |
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| Abstract: | Fibroblast growth factors (FGFs) and their receptors are expressed in a variety of mammalian tissues, playing a role in development and cell proliferation. While analyzing human sperm motility, we found that sperm treated with endo-β-galactosidase (EBG), which specifically hydrolyzes poly-N-acetyllactosamine type glycans (polyLacs), enhanced motility. Mass spectrometry analysis revealed that sperm-associated polyLacs are heavily fucosylated, consistent with Lewis Y antigen. Immunohistochemistry of epididymis using an anti-Lewis Y antibody before and after EBG treatment suggested that polyLacs carrying the Lewis Y epitope are synthesized in epididymal epithelia and secreted to seminal fluid. EBG-treated sperm elevated cAMP levels and calcium influx, indicating activation of fibroblast growth factor signaling. Seminal fluid polyLacs bound to FGFs in vitro, and impaired FGF-mediated signaling in HEK293T cells. |
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| Keywords: | Tyrosine phosphorylation Keratan sulfate Glycan array MALDI-MS Heparin |
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