title: GRK6 regulates ROS response and maintains hematopoietic stem cell self-renewal.
abstract: G protein-coupled receptor kinases (GRKs) are critically involved in immune response through regulation of cytokine receptors in mature leukocytes, but their role in hematopoiesis is largely unknown. Here, we demonstrate that GRK6 knockout (GRK6-/-) mice exhibit lymphocytopenia, loss of the hematopoietic stem cell (HSC) and multiple progenitor populations. GRK6 deficiency leads to compromised lymphoid differentiation, largely owing to the impairment of HSC self-renewal. Transcriptome and proteomic analysis suggest that GRK6 is involved in reactive oxygen species signaling. GRK6 could interact with DNA-PKcs (DNA-dependent protein kinase, catalytic subunit) and regulate its phosphorylation. Moreover, reactive oxygen species scavenger α-lipoic acid administration could partially rescue the loss of HSC in GRK6-/-mice. Our work demonstrates the importance of GRK6 in regulation of HSC self-renewal and reveals its potential role in participation of stress response.
authors.affiliation: The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Qiumin
authors.initials: Q
authors.lastname: Le
authors.affiliation: The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Yao
authors.affiliation: The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Yuejun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Yan
authors.affiliation: The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Cao
authors.initials: C
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Man
authors.initials: M
authors.lastname: Yuan
authors.affiliation: The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ma
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D000066673:Cell Self Renewal; D051747:DNA-Activated Protein Kinase / Q000378:metabolism; D054768:G-Protein-Coupled Receptor Kinases / Q000378:metabolism*; D017353:Gene Deletion; D057809:HEK293 Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000201:enzymology*; D006801:Humans; D019169:Jurkat Cells; D008231:Lymphopenia / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D051747:DNA-Activated Protein Kinase; D054768:G-Protein-Coupled Receptor Kinases; C089176:G-protein-coupled receptor kinase 6