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First published online April 23, 2007
doi: 10.1242/10.1242/jcs.001230

Journal of Cell Science 120, 1521-1528 (2007)
Published by The Company of Biologists 2007
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Research Article

YWK-II protein as a novel Go-coupled receptor for Müllerian inhibiting substance in cell survival

Xueqian Yin1,*, Songying Ouyang1,*, Wenming Xu2,*, Xiaopeng Zhang1, Kin Lam Fok2, Hau Yan Wong2, Jiaping Zhang2, Xiaobo Qiu1, Shiying Miao1, Hsiao Chang Chan2,{ddagger} and Linfang Wang1,{ddagger}

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

{ddagger} Authors for correspondence (e-mail: wanglf{at}ms.imicams.ac.cn; hsiaocchan{at}cuhk.edu.hk)

Accepted 6 March 2007

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.

Key words: MIS, YWK-II protein, APLP2, CHO, Sperm viability, Go, Extracellular signal-regulated kinase (ERK), Cell survival






© The Company of Biologists Ltd 2007