YWK-II protein as a novel Go-coupled receptor for Müllerian inhibiting substance in cell survival
Author:
Yin Xueqian1, Ouyang Songying1, Xu Wenming2, Zhang Xiaopeng1, Fok Kin Lam2, Wong Hau Yan2, Zhang Jiaping2, Qiu Xiaobo1, Miao Shiying1, Chan Hsiao Chang2, Wang Linfang1
Affiliation:
1. National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China 2. Epithelial Cell Biology Research Center, Li Ka Shing Institute of Health Sciences, Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
Abstract
Müllerian inhibiting substance (MIS) has recently been implicated in multiple cellular functions including promotion of cell survival, but the receptor(s) and signaling pathways involved remain elusive. We have investigated the possibility of YWK-II protein, previously shown to interact physically with MIS and Go protein, being a receptor mediating the cell survival effect of MIS. In YWK-II-overexpressing CHO cells, MIS activates the Go-coupled ERK1/2 signaling pathway and promotes cell survival with altered levels of p53 and caspase-3. YWK-II antibody is found to interfere with the ability of MIS to promote viability of mouse sperm and affect MIS-activated ERK1/2 phosphorylation. In vivo studies involving injection of YWK-II antibody into the seminiferous tubule of the mouse testis, where MIS is known to be produced, show significant reduction in the sperm count with accumulation of p53 and cleaved caspase-3 in testicular nuclei. Taken together, the present study has demonstrated a new Go-coupled receptor for MIS in mediating ERK1/2 activation leading to anti-apoptotic activity or cell survival.
Publisher
The Company of Biologists
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