scholarly journals Ral signals through a MAP4 Kinase-p38 MAP kinase cascade in C. elegans cell fate patterning

2018 ◽  
Author(s):  
Hanna Shin ◽  
Rebecca E.W. Kaplan ◽  
Tam Duong ◽  
Razan Fakieh ◽  
David J. Reiner
Keyword(s):  
Map Kinase ◽  
Cell Fate ◽  
P38 Map Kinase ◽  
High Dose ◽  
C Elegans ◽  
Oncogenic Ras ◽  
Map Kinase Cascade ◽  
Kinase Cascade ◽  
Vulval Precursor Cell

SummaryC. elegans vulval precursor cell (VPC) fates are patterned by an EGF gradient. High dose EGF induces 1° VPC fate, while lower dose EGF contributes to 2° fate in support of LIN-12/Notch. We previously showed that the EGF 2°-promoting signal is mediated by LET-60/Ras switching effectors, from the canonical Raf-MEK-ERK MAP kinase cascade that promotes 1° fate to the non-canonical RalGEF-Ral that promotes 2° fate. Of oncogenic Ras effectors, RalGEF-Ral is by far the least well-understood. We use genetic analysis to identify an effector cascade downstream of C. elegans RAL-1/Ral, starting with an established Ral binding partner, Exo84 of the exocyst complex. Additionally, RAL-1 signals through GCK-2, a CNH domain-containing MAP4 kinase, and PMK-1/p38 MAP kinase cascade to promote 2° fate. Our study delineates a Ral-dependent developmental signaling cascade in vivo, thus providing the mechanism by which lower EGF dose is transduced.

scholarly journals Ral Signals through a MAP4 Kinase-p38 MAP Kinase Cascade in C. elegans Cell Fate Patterning

Cell Reports ◽  
2018 ◽  
Vol 24 (10) ◽  
pp. 2669-2681.e5 ◽  
Author(s):  
Hanna Shin ◽  
Rebecca E.W. Kaplan ◽  
Tam Duong ◽  
Razan Fakieh ◽  
David J. Reiner
Keyword(s):  
Map Kinase ◽  
Cell Fate ◽  
P38 Map Kinase ◽  
C Elegans ◽  
Map Kinase Cascade ◽  
Kinase Cascade

scholarly journals Mapping of a Yeast G Protein βγ Signaling Interaction

Genetics ◽  
1998 ◽  
Vol 150 (4) ◽  
pp. 1407-1417 ◽  
Author(s):  
Simon J Dowell ◽  
Anne L Bishop ◽  
Susan L Dyos ◽  
Andrew J Brown ◽  
Malcolm S Whiteway
Keyword(s):  
Signal Transduction ◽  
Map Kinase ◽  
G Protein ◽  
Coiled Coil ◽  
Receptor Activation ◽  
Temperature Sensitive ◽  
Hydrophobic Residues ◽  
Map Kinase Cascade ◽  
Kinase Cascade

Abstract The mating pathway of Saccharomyces cerevisiae is widely used as a model system for G protein-coupled receptor-mediated signal transduction. Following receptor activation by the binding of mating pheromones, G protein βγ subunits transmit the signal to a MAP kinase cascade, which involves interaction of Gβ (Ste4p) with the MAP kinase scaffold protein Ste5p. Here, we identify residues in Ste4p required for the interaction with Ste5p. These residues define a new signaling interface close to the Ste20p binding site within the Gβγ coiled-coil. Ste4p mutants defective in the Ste5p interaction interact efficiently with Gpa1p (Gα) and Ste18p (Gγ) but cannot function in signal transduction because cells expressing these mutants are sterile. Ste4 L65S is temperature-sensitive for its interaction with Ste5p, and also for signaling. We have identified a Ste5p mutant (L196A) that displays a synthetic interaction defect with Ste4 L65S, providing strong evidence that Ste4p and Ste5p interact directly in vivo through an interface that involves hydrophobic residues. The correlation between disruption of the Ste4p-Ste5p interaction and sterility confirms the importance of this interaction in signal transduction. Identification of the Gβγ coiled-coil in Ste5p binding may set a precedent for Gβγ-effector interactions in more complex organisms.

Identification of Op18/stathmin as a potential target of ASK1-p38 MAP kinase cascade

2005 ◽  
Vol 206 (2) ◽  
pp. 363-370 ◽  
Author(s):  
Kenji Mizumura ◽  
Kohsuke Takeda ◽  
Shu Hashimoto ◽  
Takashi Horie ◽  
Hidenori Ichijo
Keyword(s):  
Map Kinase ◽  
P38 Map Kinase ◽  
Potential Target ◽  
Map Kinase Cascade ◽  
Kinase Cascade

Caveolin-mediated regulation of signaling along the p42/44 MAP kinase cascade in vivo

FEBS Letters ◽  
1998 ◽  
Vol 428 (3) ◽  
pp. 205-211 ◽  
Author(s):  
Jeffrey A. Engelman ◽  
Caryn Chu ◽  
Anning Lin ◽  
Hanjoong Jo ◽  
Tsuneya Ikezu ◽  
...  
Keyword(s):  
Map Kinase ◽  
Map Kinase Cascade ◽  
Kinase Cascade

scholarly journals Interaction of Rac Exchange Factors Tiam1 and Ras-GRF1 with a Scaffold for the p38 Mitogen-Activated Protein Kinase Cascade

2002 ◽  
Vol 22 (12) ◽  
pp. 4073-4085 ◽  
Author(s):  
Rachel J. Buchsbaum ◽  
Beth A. Connolly ◽  
Larry A. Feig
Keyword(s):  
Map Kinase ◽  
P38 Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Nucleotide Exchange ◽  
Rac Gtpase ◽  
Signaling Specificity ◽  
Map Kinase Cascade ◽  
Mitogen Activated Protein ◽  
Kinase Cascade ◽  
In Cells

ABSTRACT Tiam1 and Ras-GRF1 are guanine nucleotide exchange factors (GEFs) that activate the Rac GTPase. The two GEFs have similar N-terminal regions containing pleckstrin homology domains followed by coiled-coils and additional sequences that function together to allow regulated GEF activity. Here we show that this N-terminal region of both proteins binds to the scaffold protein IB2/JIP2. IB2/JIP2 is a scaffold for the p38 mitogen-activated protein (MAP) kinase cascade because it binds to the Rac target MLK3, the MAP kinase kinase MKK3, and the p38 MAP kinase. Expression of IB2/JIP2 in cells potentiates the ability of Tiam1 or Ras-GRF1 to activate the p38 MAP kinase cascade but not the Jnk MAP kinase cascade. In addition, Tiam1 or Ras-GRF1 binding to IB2/JIP2 increases the association of the components of the p38 MAP kinase signaling cassette with IB2/JIP2 in cells and activates scaffold-associated p38. These findings imply that Tiam1 and Ras-GRF1 can contribute to Rac signaling specificity by their ability to form a complex with a scaffold that binds components of one of the many known Rac effector pathways.

scholarly journals Legionella pneumophila Suppresses Macrophage Interleukin-12 Production by Activating the p42/44 Mitogen-Activated Protein Kinase Cascade

2003 ◽  
Vol 71 (11) ◽  
pp. 6672-6675 ◽  
Author(s):  
Kazuto Matsunaga ◽  
Hiroyuki Yamaguchi ◽  
Thomas W. Klein ◽  
Herman Friedman ◽  
Yoshimasa Yamamoto
Keyword(s):  
Map Kinase ◽  
Legionella Pneumophila ◽  
Kinase Inhibitors ◽  
Selective Inhibition ◽  
P38 Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Interleukin 12 ◽  
Map Kinase Cascade ◽  
Mitogen Activated Protein ◽  
Kinase Cascade

ABSTRACT A possible involvement of the mitogen-activated protein (MAP) kinase cascade in the inhibition of macrophage interleukin-12 (IL-12) production by Legionella pneumophila infection was examined. The results of MAP kinase inhibition by p42/44 and p38 MAP kinase inhibitors and of p42/44 MAP kinase activity assays indicate that L. pneumophila infection of macrophages causes a selective inhibition of lipopolysaccharide-induced IL-12 production by activating the p42/44 MAP kinase cascade. In addition, it was also revealed that the p38 MAP kinase may be important for the production of IL-12 but not for the inhibition caused by L. pneumophila infection.

scholarly journals Derepressed Hyphal Growth and Reduced Virulence in a VH1 Family-related Protein Phosphatase Mutant of the Human PathogenCandida albicans

1997 ◽  
Vol 8 (12) ◽  
pp. 2539-2551 ◽  
Author(s):  
Csilla Csank ◽  
Constantin Makris ◽  
Sylvain Meloche ◽  
Klaus Schröppel ◽  
Martin Röllinghoff ◽  
...  
Keyword(s):  
Map Kinase ◽  
Cell Fate ◽  
Map Kinases ◽  
Hyphal Growth ◽  
Filamentous Form ◽  
Cell Fate Decisions ◽  
Map Kinase Cascade ◽  
Dual Specificity ◽  
Kinase Cascade

Mitogen-activated protein (MAP) kinases are pivotal components of eukaryotic signaling cascades. Phosphorylation of tyrosine and threonine residues activates MAP kinases, but either dual-specificity or monospecificity phosphatases can inactivate them. The Candida albicans CPP1 gene, a structural member of the VH1 family of dual- specificity phosphatases, was previously cloned by its ability to block the pheromone response MAP kinase cascade in Saccharomyces cerevisiae. Cpp1p inactivated mammalian MAP kinases in vitro and acted as a tyrosine-specific enzyme. In C. albicansa MAP kinase cascade can trigger the transition from the budding yeast form to a more invasive filamentous form. Disruption of theCPP1 gene in C. albicans derepressed the yeast to hyphal transition at ambient temperatures, on solid surfaces. A hyphal growth rate defect under physiological conditions in vitro was also observed and could explain a reduction in virulence associated with reduced fungal burden in the kidneys seen in a systemic mouse model. A hyper-hyphal pathway may thus have some detrimental effects onC. albicans cells. Disruption of the MAP kinase homologue CEK1 suppressed the morphological effects of the CPP1 disruption in C. albicans. The results presented here demonstrate the biological importance of a tyrosine phosphatase in cell-fate decisions and virulence in C. albicans.

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