Germ Line Deletion Reveals a Nonessential Role of Atypical Mitogen-Activated Protein Kinase 6/Extracellular Signal-Regulated Kinase 3
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Germ Line Deletion Reveals a Nonessential Role of Atypical Mitogen-Activated Protein Kinase 6/Extracellular Signal-Regulated Kinase 3. / Ronkina, N; Schuster-Gossler, K; Hansmann, F; Kunze-Schumacher, H; Sandrock, I; Yakovleva, T; Lafera, J; Baumgärtner, W; Krueger, A; Prinz, I; Gossler, A; Kotlyarov, A; Gaestel, M.
In: MOL CELL BIOL, Vol. 39, No. 6, 15.03.2019.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Germ Line Deletion Reveals a Nonessential Role of Atypical Mitogen-Activated Protein Kinase 6/Extracellular Signal-Regulated Kinase 3
AU - Ronkina, N
AU - Schuster-Gossler, K
AU - Hansmann, F
AU - Kunze-Schumacher, H
AU - Sandrock, I
AU - Yakovleva, T
AU - Lafera, J
AU - Baumgärtner, W
AU - Krueger, A
AU - Prinz, I
AU - Gossler, A
AU - Kotlyarov, A
AU - Gaestel, M
N1 - Copyright © 2019 American Society for Microbiology.
PY - 2019/3/15
Y1 - 2019/3/15
N2 - Mitogen-activated protein kinase 6/extracellular signal-regulated kinase 3 (MAPK6/ERK3) is an atypical member of the MAPKs. An essential role has been suggested by the perinatal lethal phenotype of ERK3 knockout mice carrying a lacZ insertion in exon 2 due to pulmonary dysfunction and by defects in function, activation, and positive selection of T cells. To study the role of ERK3 in vivo, we generated mice carrying a conditional Erk3 allele with exon 3 flanked by loxP sites. Loss of ERK3 protein was validated after deletion of Erk3 in the female germ line using zona pellucida 3 (Zp3)-cre and a clear reduction of the protein kinase MK5 is detected, providing the first evidence for the existence of the ERK3/MK5 signaling complex in vivo In contrast to the previously reported Erk3 knockout phenotype, these mice are viable and fertile and do not display pulmonary hypoplasia, acute respiratory failure, abnormal T-cell development, reduction of thymocyte numbers, or altered T-cell selection. Hence, ERK3 is dispensable for pulmonary and T-cell functions. The perinatal lethality and lung and T-cell defects of the previous ERK3 knockout mice are likely due to ERK3-unrelated effects of the inserted lacZ-neomycin resistance cassette. The knockout mouse of the closely related atypical MAPK ERK4/MAPK4 is also normal, suggesting redundant functions of both protein kinases.
AB - Mitogen-activated protein kinase 6/extracellular signal-regulated kinase 3 (MAPK6/ERK3) is an atypical member of the MAPKs. An essential role has been suggested by the perinatal lethal phenotype of ERK3 knockout mice carrying a lacZ insertion in exon 2 due to pulmonary dysfunction and by defects in function, activation, and positive selection of T cells. To study the role of ERK3 in vivo, we generated mice carrying a conditional Erk3 allele with exon 3 flanked by loxP sites. Loss of ERK3 protein was validated after deletion of Erk3 in the female germ line using zona pellucida 3 (Zp3)-cre and a clear reduction of the protein kinase MK5 is detected, providing the first evidence for the existence of the ERK3/MK5 signaling complex in vivo In contrast to the previously reported Erk3 knockout phenotype, these mice are viable and fertile and do not display pulmonary hypoplasia, acute respiratory failure, abnormal T-cell development, reduction of thymocyte numbers, or altered T-cell selection. Hence, ERK3 is dispensable for pulmonary and T-cell functions. The perinatal lethality and lung and T-cell defects of the previous ERK3 knockout mice are likely due to ERK3-unrelated effects of the inserted lacZ-neomycin resistance cassette. The knockout mouse of the closely related atypical MAPK ERK4/MAPK4 is also normal, suggesting redundant functions of both protein kinases.
KW - Animals
KW - Female
KW - Gene Deletion
KW - Germ Cells
KW - Germ-Line Mutation
KW - Intracellular Signaling Peptides and Proteins/genetics
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Mitogen-Activated Protein Kinase 6/genetics
KW - Protein Binding
KW - Protein-Serine-Threonine Kinases/genetics
KW - Sequence Deletion
KW - Signal Transduction
KW - T-Lymphocytes/metabolism
KW - Zona Pellucida
U2 - 10.1128/MCB.00516-18
DO - 10.1128/MCB.00516-18
M3 - SCORING: Journal article
C2 - 30642948
VL - 39
JO - MOL CELL BIOL
JF - MOL CELL BIOL
SN - 0270-7306
IS - 6
ER -