Germ Line Deletion Reveals a Nonessential Role of Atypical Mitogen-Activated Protein Kinase 6/Extracellular Signal-Regulated Kinase 3

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 -