PMID- 10209122
OWN - NLM
STAT- MEDLINE
DCOM- 19990511
LR  - 20190728
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 9
IP  - 7
DP  - 1999 Apr 8
TI  - Embryonic death of Mek1-deficient mice reveals a role for this kinase in
      angiogenesis in the labyrinthine region of the placenta.
PG  - 369-72
AB  - Mek is a dual-specificity kinase that activates the
      extracellular-signal-regulated (Erk) mitogen-activated protein (MAP) kinases upon
      agonist binding to receptors. The Erk MAP kinase cascade is involved in cell-fate
      determination in many organisms. In mammals, this pathway is proposed to regulate
      cell growth and differentiation. Genetic studies have shown that although a
      single mek gene is present in Caenorhabditis elegans, Drosophila and Xenopus, two
      mek homologs, Mek1 and Mek2, are present in the mammalian cascade. In the present
      study, we describe a mutant mouse line in which the mek1 gene has been disrupted 
      by insertional mutagenesis. The null mutation was recessive lethal, as the
      homozygous mutant embryos died at 10.5 days of gestation. Histopathological
      analyses revealed a reduction in vascularization of the placenta that was due to 
      a marked decrease of vascular endothelial cells in the labyrinthine region. The
      failure to establish a functional placenta probably explains the death of the
      mek1-/- embryos. Cell-migration assays indicated that mek1-/- fibroblasts could
      not be induced to migrate by fibronectin, although the levels of Mek2 protein and
      Erk activation were normal. Re-expression of Mek1 in the mutant mouse embryonic
      fibroblasts (MEFs) restored their ability to migrate. Our findings provide
      genetic evidence that establishes the unique role played by Mek1 in signal
      transduction. They also suggest that mek1 function is required for normal
      response to angiogenic signals that might promote vascularization of the
      labyrinthine region of the placenta.
FAU - Giroux, S
AU  - Giroux S
AD  - Centre de recherche en cancerologie de l'Universite Laval, Centre Hospitalier
      Universitaire de Quebec, Pavillon L'Hotel-Dieu de Quebec, 9, a rue McMahon,
      Quebec, Canada, G1R 2J6.
FAU - Tremblay, M
AU  - Tremblay M
FAU - Bernard, D
AU  - Bernard D
FAU - Cardin-Girard, J F
AU  - Cardin-Girard JF
FAU - Aubry, S
AU  - Aubry S
FAU - Larouche, L
AU  - Larouche L
FAU - Rousseau, S
AU  - Rousseau S
FAU - Huot, J
AU  - Huot J
FAU - Landry, J
AU  - Landry J
FAU - Jeannotte, L
AU  - Jeannotte L
FAU - Charron, J
AU  - Charron J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Fibronectins)
RN  - 0 (Receptors, Growth Factor)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (Map2k1 protein, mouse)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Animals
MH  - Blood Vessels/embryology/*metabolism
MH  - Cell Movement/drug effects/genetics
MH  - Embryo, Mammalian/cytology/enzymology
MH  - Female
MH  - Fetal Death/*genetics
MH  - Fibronectins/pharmacology
MH  - Gene Expression Regulation, Developmental
MH  - Histocytochemistry
MH  - In Situ Hybridization
MH  - MAP Kinase Kinase 1
MH  - Mice
MH  - Mice, Knockout
MH  - *Mitogen-Activated Protein Kinase Kinases
MH  - Neovascularization, Physiologic/genetics
MH  - Placenta/*physiology
MH  - Pregnancy
MH  - Protein-Serine-Threonine Kinases/*deficiency/genetics
MH  - Protein-Tyrosine Kinases/*deficiency/genetics
MH  - Receptor Protein-Tyrosine Kinases/genetics
MH  - Receptors, Growth Factor/genetics
MH  - Receptors, Vascular Endothelial Growth Factor
EDAT- 1999/04/21 00:00
MHDA- 1999/04/21 00:01
CRDT- 1999/04/21 00:00
PHST- 1999/04/21 00:00 [pubmed]
PHST- 1999/04/21 00:01 [medline]
PHST- 1999/04/21 00:00 [entrez]
AID - S0960-9822(99)80164-X [pii]
AID - 10.1016/s0960-9822(99)80164-x [doi]
PST - ppublish
SO  - Curr Biol. 1999 Apr 8;9(7):369-72. doi: 10.1016/s0960-9822(99)80164-x.