The Experts below are selected from a list of 184620 Experts worldwide ranked by ideXlab platform

Jacques Pouyssegur - One of the best experts on this subject based on the ideXlab platform.

Sylvain Meloche - One of the best experts on this subject based on the ideXlab platform.

  • the erk1 2 mitogen activated Protein Kinase pathway as a master regulator of the g1 to s phase transition
    2007
    Co-Authors: Sylvain Meloche, Jacques Pouyssegur
    Abstract:

    The ERK1/2 Mitogen-Activated Protein Kinase pathway as a master regulator of the G1- to S-phase transition

  • an essential function of the mitogen activated Protein Kinase erk2 in mouse trophoblast development
    2003
    Co-Authors: Marc K Sabaelleil, Francis D J Vella, Bertrand Vernay, Laure Voisin, Lan Chen, Nathalie Labrecque, Siewlan Ang, Sylvain Meloche
    Abstract:

    The closely related Mitogen-Activated Protein Kinase isoforms extracellular signal-regulated Kinase 1 (ERK1) and ERK2 have been implicated in the control of cell proliferation, differentiation and survival. However, the specific in vivo functions of the two ERK isoforms remain to be analysed. Here, we show that disruption of the Erk2 locus leads to embryonic lethality early in mouse development after the implantation stage. Erk2 mutant embryos fail to form the ectoplacental cone and extra-embryonic ectoderm, which give rise to mature trophoblast derivatives in the fetus. Analysis of chimeric embryos showed that Erk2 functions in a cell-autonomous manner during the development of extra-embryonic cell lineages. We also found that both Erk2 and Erk1 are widely expressed throughout early-stage embryos. The inability of Erk1 to compensate for Erk2 function suggests a specific function for Erk2 in normal trophoblast development in the mouse, probably in regulating the proliferation of polar trophectoderm cells.

Haibin Kuang - One of the best experts on this subject based on the ideXlab platform.

  • kisspeptin stimulates progesterone secretion via the erk1 2 mitogen activated Protein Kinase signaling pathway in rat luteal cells
    2013
    Co-Authors: Jing Peng, Min Tang, Baoping Zhang, Peng Zhang, Ting Zhong, Teng Zong, Bei Yang, Haibin Kuang
    Abstract:

    Objective To observe the effect of kisspeptin on the endocrine function of rat luteal cells. Design Experimental animal study. Setting Research institute laboratory. Animal(s) Immature Sprague-Dawley rats. Intervention(s) The expression of kisspeptin and its receptor, GPR54, in immature rat ovaries treated with gonadotropin was observed via immunohistochemistry and real-time polymerase chain reaction. Then recombinant kisspeptin was used to examine the effect on the endocrine function of rat luteal cells. Main Outcome Measure(s) Expression and localization of kisspeptin, localization of GPR54, P and E 2 secretion, expression of steroidogenic enzymes, and phosphorylation of Erk1/2. Result(s) Real-time polymerase chain reaction indicated that ovarian KiSS-1 mRNA levels increased significantly, showing a peak at the luteal period in gonadotropin-primed immature rats. Immunostaining analysis showed that after gonadotropin treatment, kisspeptin was strongly localized in theca cells, the interstitial compartment, and the corpus luteum and that GPR54 Protein was clearly detected in the corpus luteum of rat ovaries. In cultured luteal cells, kisspeptin treatment augmented basal and hCG-induced P levels but not E 2 production, with concomitant increases detected in the transcript levels of key steroidogenic enzymes (StAR, CYP11A, and 3β-HSD). Furthermore, treatment with kisspeptin increased the phosphorylation of Erk1/2 Mitogen-Activated Protein Kinase in cultured luteal cells. Conclusion(s) The kisspeptin/GPR54 signaling system could stimulate P secretion in rat luteal cells via the Erk1/2 Mitogen-Activated Protein Kinase signaling pathway, suggesting an important role for the function of the corpus luteum.

Jon W Lomasney - One of the best experts on this subject based on the ideXlab platform.

  • a novel bifunctional phospholipase c that is regulated by gα12and stimulates the ras mitogen activated Protein Kinase pathway
    2001
    Co-Authors: Isabel Lopez, Jirong Ding, Heidi E Hamm, Jon W Lomasney
    Abstract:

    Abstract Three families of phospholipase C (PI-PLCβ, γ, and δ) are known to catalyze the hydrolysis of polyphosphoinositides such as phosphatidylinositol 4,5-bisphosphate (PIP2) to generate the second messengers inositol 1,4,5 trisphosphate and diacylglycerol, leading to a cascade of intracellular responses that result in cell growth, cell differentiation, and gene expression. Here we describe the founding member of a novel, structurally distinct fourth family of PI-PLC. PLCe not only contains conserved catalytic (X and Y) and regulatory domains (C2) common to other eukaryotic PLCs, but also contains two Ras-associating (RA) domains and a Ras guanine nucleotide exchange factor (RasGEF) motif. PLCe hydrolyzes PIP2, and this activity is stimulated selectively by a constitutively active form of the heterotrimeric G Protein Gα12. PLCe and a mutant (H1144L) incapable of hydrolyzing phosphoinositides promote formation of GTP-Ras. Thus PLCe is a RasGEF. PLCe, the mutant H1144L, and the isolated GEF domain activate the Mitogen-Activated Protein Kinase pathway in a manner dependent on Ras but independent of PIP2 hydrolysis. Our findings demonstrate that PLCe is a novel bifunctional enzyme that is regulated by the heterotrimeric G Protein Gα12 and activates the small G Protein Ras/Mitogen-Activated Protein Kinase signaling pathway.

  • a novel bifunctional phospholipase c that is regulated by gα12 and stimulates the ras mitogen activated Protein Kinase pathway
    2001
    Co-Authors: Isabel Lopez, Jirong Ding, Heidi E Hamm, Eric C Mak, Jon W Lomasney
    Abstract:

    Three families of phospholipase C (PI-PLCβ, γ, and δ) are known to catalyze the hydrolysis of polyphosphoinositides such as phosphatidylinositol 4,5-bisphosphate (PIP2) to generate the second messengers inositol 1,4,5 trisphosphate and diacylglycerol, leading to a cascade of intracellular responses that result in cell growth, cell differentiation, and gene expression. Here we describe the founding member of a novel, structurally distinct fourth family of PI-PLC. PLCe not only contains conserved catalytic (X and Y) and regulatory domains (C2) common to other eukaryotic PLCs, but also contains two Ras-associating (RA) domains and a Ras guanine nucleotide exchange factor (RasGEF) motif. PLCe hydrolyzes PIP2, and this activity is stimulated selectively by a constitutively active form of the heterotrimeric G Protein Gα12. PLCe and a mutant (H1144L) incapable of hydrolyzing phosphoinositides promote formation of GTP-Ras. Thus PLCe is a RasGEF. PLCe, the mutant H1144L, and the isolated GEF domain activate the Mitogen-Activated Protein Kinase pathway in a manner dependent on Ras but independent of PIP2 hydrolysis. Our findings demonstrate that PLCe is a novel bifunctional enzyme that is regulated by the heterotrimeric G Protein Gα12 and activates the small G Protein Ras/Mitogen-Activated Protein Kinase signaling pathway.

Masanori Aikawa - One of the best experts on this subject based on the ideXlab platform.

  • free cholesterol accumulation in macrophage membranes activates toll like receptors and p38 mitogen activated Protein Kinase and induces cathepsin k
    2009
    Co-Authors: Yu Sun, Minako Ishibashi, Tracie A Seimon, Mingsum Lee, Sudarshana M Sharma, Katherine A Fitzgerald, Andriy O Samokhin, Yibin Wang, Scott Sayers, Masanori Aikawa
    Abstract:

    The molecular events linking lipid accumulation in atherosclerotic plaques to complications such as aneurysm formation and plaque disruption are poorly understood. BALB/c-Apoe(-/-) mice bearing a null mutation in the Npc1 gene display prominent medial erosion and atherothrombosis, whereas their macrophages accumulate free cholesterol in late endosomes and show increased cathepsin K (Ctsk) expression. We now show increased cathepsin K immunostaining and increased cysteinyl Proteinase activity using near infrared fluorescence imaging over proximal aortas of Apoe(-/-), Npc1(-/-) mice. In mechanistic studies, cholesterol loading of macrophage plasma membranes (cyclodextrin-cholesterol) or endosomal system (AcLDL+U18666A or Npc1 null mutation) activated Toll-like receptor (TLR) signaling, leading to sustained phosphorylation of p38 Mitogen-Activated Protein Kinase and induction of p38 targets, including Ctsk, S100a8, Mmp8, and Mmp14. Studies in macrophages from knockout mice showed major roles for TLR4, following plasma membrane cholesterol loading, and for TLR3, after late endosomal loading. TLR signaling via p38 led to phosphorylation and activation of the transcription factor Microphthalmia transcription factor, acting at E-box elements in the Ctsk promoter. These studies suggest that free cholesterol enrichment of either plasma or endosomal membranes in macrophages leads to activation of signaling via various TLRs, prolonged p38 Mitogen-Activated Protein Kinase activation, and induction of Mmps, Ctsk, and S100a8, potentially contributing to plaque complications.

  • free cholesterol accumulation in macrophage membranes activates toll like receptors and p38 mitogen activated Protein Kinase and induces cathepsin k
    2009
    Co-Authors: Minako Ishibashi, Tracie A Seimon, Sudarshana M Sharma, Katherine A Fitzgerald, Andriy O Samokhin, Yibin Wang, Scott Sayers, Masanori Aikawa, Gray W Jerome, Michael C Ostrowski
    Abstract:

    The molecular events linking lipid accumulation in atherosclerotic plaques to complications such as aneurysm formation and plaque disruption are poorly understood. BALB/c- Apoe −/− mice bearing a null mutation in the Npc1 gene display prominent medial erosion and atherothrombosis, whereas their macrophages accumulate free cholesterol in late endosomes and show increased cathepsin K ( Ctsk ) expression. We now show increased cathepsin K immunostaining and increased cysteinyl Proteinase activity using near infrared fluorescence imaging over proximal aortas of Apoe −/− , Npc1 −/− mice. In mechanistic studies, cholesterol loading of macrophage plasma membranes (cyclodextrin–cholesterol) or endosomal system (AcLDL+U18666A or Npc1 null mutation) activated Toll-like receptor (TLR) signaling, leading to sustained phosphorylation of p38 Mitogen-Activated Protein Kinase and induction of p38 targets, including Ctsk , S100a8 , Mmp8 , and Mmp14 . Studies in macrophages from knockout mice showed major roles for TLR4, following plasma membrane cholesterol loading, and for TLR3, after late endosomal loading. TLR signaling via p38 led to phosphorylation and activation of the transcription factor Microphthalmia transcription factor, acting at E-box elements in the Ctsk promoter. These studies suggest that free cholesterol enrichment of either plasma or endosomal membranes in macrophages leads to activation of signaling via various TLRs, prolonged p38 Mitogen-Activated Protein Kinase activation, and induction of Mmps , Ctsk , and S100a8 , potentially contributing to plaque complications.