Mitogen-activated protein (MAP) kinases, also known as extracellular signal-regulated kinases (ERKs) , are thought to act as an integration point for multiple biochemical signals because they are activated by a wide
variety of extracellular signals, are rapidly phosphorylated on threonine and tyrosine residues, and are highly conserved
in evolution . A critical protein kinase lies upstream of MAP kinase and stimulates the enzymatic activity of MAP kinase. Crews et al. (1992) cloned a mouse cDNA, denoted Mek1 (for Map/Erk kinase-1) by them, that
encodes a member of this protein kinase family.
NCBI Summary:
The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development.
Chen DB, et al reported that prostaglandin F2alpha stimulates the
Raf/MEK1/mitogen-activated protein kinase signaling cascade in
bovine luteal cells.
Three isoforms of the Raf family of oncoprotein kinases (A-Raf, B-Raf, and Raf-1
or c-Raf) were detected in bovine luteal cells. Raf-1 and B-Raf, but not A-Raf,
were activated by PGF2alpha (1 microM) and the pharmacological PKC activator
phorbol myristate acetate (PMA, 20 nM). Kinetic analysis revealed that
PGF2alpha rapidly and transiently activated Raf-1.
In vitro protein kinase assays
demonstrated that activation of Raf-1 and B-Raf resulted in the phosphorylation
and activation of MAPK kinase (MEK1), which subsequently phosphorylated p42mapk. As determined by hyperphosphorylation, tyrosine phosphorylation, and
enzymatic activity, p42mapk and p44mapk were rapidly and transiently activated
by both PGF2alpha (1 microM) and PMA (20 nM). Additionally, both PGF2alpha
(1 microM) and PMA (20 nM) stimulated phosphorylation of Raf-1, MEK1, and
p42mapk in 32P-labeled cells. The data demonstrate that PGF2alpha activates the
Raf/MEK1/p42/44mapk signaling cascade in bovine luteal cells and that the
actions of PGF2alpha are mimicked by the PKC activator PMA. Activation of the
Raf/MEK1/MAPK signaling cascade by PGF2alpha in luteal cells provides a
mechanism to transduce signals initiated by PGF2alpha receptors on the cell
surface into the nucleus.
Gene whose expression is detected by cDNA array hybridization: transporters, signal transduction Rozenn Dalbi?Tran and Pascal Mermilloda
Antibody Microarray Analyses of Signal Transduction Protein Expression and Phosphorylation during Porcine Oocyte Maturation. Pelech S et al. Kinex antibody microarray analyses was used to investigate the regulation of 188 protein kinases, 24 protein phosphatases, and 170 other regulatory proteins during meiotic maturation of immature germinal vesicle (GV+) pig oocytes to maturing oocytes that had completed meiosis I (MI), and fully mature oocytes arrested at metaphase of meiosis II (MII). Increases in apparent protein levels of protein kinases accounted for most of the detected changes during the GV to MI transition, whereas reduced protein kinase levels and increased protein phosphorylation characterized the MI to MII transition. During the MI to MII period, many of the MI-associated increased levels of the proteins and phosphosites were completely or partially reversed. The regulation of these proteins were also examined in parallel during the meiotic maturation of bovine, frog, and sea star oocytes with the Kinex antibody microarray. Western blotting analyses confirmed altered expression levels of Bub1A, IRAK4, MST2, PP4C, and Rsk2, and the phosphorylation site changes in the kinases Erk5 (T218 + Y220), FAK (S722), GSK3-beta (Y216), MEK1 (S217 + S221) and PKR1 (T451), and nucleophosmin/B23 (S4) during pig oocyte maturation.
Expression regulated by
FSH, Eicosanoids
Comment
Ovarian localization
Oocyte, Luteal cells
Comment
You-Qiang Su et al 2001 reported hormone-Induced but Not Spontaneous Meiotic Resumption of Mouse Oocytes.
The
present experiments were conducted to investigate the possible role of MAP
kinase in FSH-induced and spontaneous
oocyte meiotic resumption in the mouse. MAP kinase kinase (MAPKK, MEK)
inhibitor, PD98059 or U0126, produced
a dose-dependent inhibitory effect on both FSH-induced oocyte meiotic
resumption and MAP kinase activation in the
oocytes. However, the same inhibitor did not block spontaneous meiotic
resumption of either denuded or cumulus
cell-enclosed mouse oocytes, despite the activity of MAP kinase being totally
inhibited.
Immunoblotting the oocytes and
the cumulus cells with the anti-active MAP kinase antibody showed that MAP
kinase activity in the oocytes was
detected at 8 h of FSH treatment, prior to germinal vesicle breakdown and
increased as maturation progressed in the
following culture period. In the cumulus cells, MAP kinase was activated even
faster, its activity was detected at 1 h of
FSH stimulation and increased gradually until 8 h of FSH treatment, then
decreased and diminished after 12 h of FSH
action. These data demonstrated that the MEK-MAP kinase pathway is implicated
in FSH-induced but not spontaneous
oocyte meiotic resumption.