title: Functional Redundancy of ERK1 and ERK2 MAP Kinases during Development.
abstract: ERK1 and ERK2 are the effector kinases of the ERK1/2 MAP-kinase signaling pathway, which plays a central role in transducing signals controlling cell proliferation, differentiation, and survival. Deregulated activity of the ERK1/2 pathway is linked to a group of developmental syndromes and contributes to the pathogenesis of various human diseases. One fundamental question that remains unaddressed is whether ERK1 and ERK2 have evolved unique physiological functions or whether they are used redundantly to reach a threshold of global ERK activity. Here, we show that the extent of development of the mouse placenta and embryo bearing different combinations of Erk1 and Erk2 alleles is strictly correlated with total ERK1/2 activity. We further demonstrate that transgenic expression of ERK1 fully rescues the embryonic and placental developmental defects associated with the loss of ERK2. We conclude that ERK1 and ERK2 exert redundant functions in mouse development.
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Quebec QC H3T 1J4, Canada. Electronic address: christophe.fremin@inserm.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Frémin
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Quebec QC H3T 1J4, Canada.
authors.forename: Marc K
authors.initials: MK
authors.lastname: Saba-El-Leil
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Quebec QC H3T 1J4, Canada.
authors.forename: Kim
authors.initials: K
authors.lastname: Lévesque
authors.affiliation: Division of Developmental Neurobiology, MRC National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK.
authors.forename: Siew-Lan
authors.initials: SL
authors.lastname: Ang
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Quebec QC H3T 1J4, Canada; Molecular Biology Program, Université de Montréal, Montreal, Quebec QC H3T 1J4, Canada; Department of Pharmacology, Université de Montréal, Montreal, Quebec QC H3T 1J4, Canada. Electronic address: sylvain.meloche@umontreal.ca.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Meloche
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics / Q000502:physiology; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3