YWK-II protein as a novel G(o)-coupled receptor for Müllerian inhibiting substance in cell survival.
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 G(o) protein, being a receptor mediating the cell survival effect of MIS. In YWK-II-overexpressing CHO cells, MIS activates the G(o)-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 G(o)-coupled receptor for MIS in mediating ERK1/2 activation leading to anti-apoptotic activity or cell survival.
Yin
Xueqian
X
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.
Ouyang
Songying
S
Xu
Wenming
W
Zhang
Xiaopeng
X
Fok
Kin Lam
KL
Wong
Hau Yan
HY
Zhang
Jiaping
J
Qiu
Xiaobo
X
Miao
Shiying
S
Chan
Hsiao Chang
HC
Wang
Linfang
L
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D054304:Anti-Mullerian Hormone; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016466:CHO Cells; D019556:COS Cells; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D018125:Receptors, Transforming Growth Factor beta; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects; D013735:Testicular Hormones / Q000494:pharmacology*; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014162:Transfection
C084104:APLP2 protein, human; D016564:Amyloid beta-Protein Precursor; D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; D011993:Recombinant Fusion Proteins; D013735:Testicular Hormones; C084621:anti-Mullerian hormone receptor; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D054304:Anti-Mullerian Hormone; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D019206:GTP-Binding Protein alpha Subunits, Gi-Go