title: Noncanonical Activin A Signaling in PC12 Cells: A Self-Limiting Feedback Loop.
abstract: Activin A (Act A), a member of transforming growth factor-β superfamily, plays a neuroprotective role in multiple neurological diseases through Act A/Smads signal activation. Traditionally, the up-regulation of Act A gene and extracellular Act A accumulation show the signal activation as a linear pathway. However, one of our discoveries indicated that Act A could lead a loop signaling in ischemic injury. To clarify the characteristic of this loop signaling in a non-pathological state, we up-regulated the expression of Act A, monitored extracellular Act A accumulation and examined the activity of Act A signaling, which was quantified by the expression of phosphorylated Smad3 and the fluorescence intensity of Smad4 in nuclei. The results demonstrated a noncanonical Act A signal loop with self-amplifying property in PC12 cells. Further, it showed self-limiting behavior due to temporary activation and spontaneous attenuation. This periodic behavior of Act A signal loop was found to be regulated by the level of Smad anchor for receptor activation (SARA). Moreover, increased activity of Act A signal loop could promote PC12 cell proliferation and enhance the survival rate of cells to Oxygen-Glucose Deprivation. These practical discoveries will bring new insight on the functional outcome of Act A signaling in neurological diseases by the further understanding: loop signaling.
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, 130012, China.
authors.forename: Jiao-Qi
authors.initials: JQ
authors.lastname: Wang
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, 130012, China.
authors.forename: Wen-Zhao
authors.initials: WZ
authors.lastname: Liang
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, 130012, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, 130012, China.
authors.forename: Jin-Ting
authors.initials: JT
authors.lastname: He
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, 130012, China.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Liu
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, 130012, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, 130012, China.
authors.forename: Long-Xing
authors.initials: LX
authors.lastname: Xue
authors.affiliation: Research Center, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, 130012, China.
authors.forename: Qiu-Ye
authors.initials: QY
authors.lastname: Ji
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, 2699 Qianjin Street, Changchun, 130012, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, 130012, China.
authors.forename: Yan-Kun
authors.initials: YK
authors.lastname: Shao
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, 130012, China. mangjing@jlu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Mang
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, 130012, China. xuzhongxin999@aliyun.com.
authors.forename: Zhong-Xin
authors.initials: ZX
authors.lastname: Xu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D005246:Feedback; D005947:Glucose / Q000378:metabolism; D028322:Inhibin-beta Subunits / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D011994:Recombinant Proteins; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D051901:Smad4 Protein; C490811:Smad4 protein, rat; C000602391:Zfyve9 protein, rat; C103008:inhibin beta A subunit; D028322:Inhibin-beta Subunits; D005947:Glucose; D010100:Oxygen
keywords: Activin A; Signaling loop; Smad anchor for receptor activation