MAPKAP kinase MK2 maintains self-renewal capacity of haematopoietic stem cells.
The structurally related MAPK-activated protein kinases (MAPKAPKs or MKs) MK2, MK3 and MK5 are involved in multiple cellular functions, including cell-cycle control and cellular differentiation. Here, we show that after deregulation of cell-cycle progression, haematopoietic stem cells (HSCs) in MK2-deficient mice are reduced in number and show an impaired ability for competitive repopulation in vivo. To understand the underlying molecular mechanism, we dissected the role of MK2 in association with the polycomb group complex (PcG) and generated a MK2 mutant, which is no longer able to bind to PcG. The reduced ability for repopulation is rescued by re-introduction of MK2, but not by the Edr2-non-binding mutant of MK2. Thus, MK2 emerges as a regulator of HSC homeostasis, which could act through chromatin remodelling by the PcG complex.
Institute of Biochemistry, Hannover Medical School, Hannover, Germany.
Jessica
J
Schwermann
Chozhavendan
C
Rathinam
Maria
M
Schubert
Stefanie
S
Schumacher
Fatih
F
Noyan
Haruhiko
H
Koseki
Alexey
A
Kotlyarov
Christoph
C
Klein
Matthias
M
Gaestel
D000818:Animals; D005816:Genetic Complementation Test; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063146:Polycomb-Group Proteins; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism; D000099190:MAP-Kinase-Activated Kinase 2
D047908:Intracellular Signaling Peptides and Proteins; D063146:Polycomb-Group Proteins; D017346:Protein Serine-Threonine Kinases; D012097:Repressor Proteins; D000099190:MAP-Kinase-Activated Kinase 2