Ginseng (Panax quinquefolius) Attenuates Leptin-Induced Cardiac Hypertrophy through Inhibition of p115Rho Guanine Nucleotide Exchange Factor-RhoA/Rho-Associated, Coiled-Coil Containing Protein Kinase-Dependent Mitogen-Activated Protein Kinase Pathway Activation

2011 ◽  
Vol 339 (3) ◽  
pp. 746-756 ◽  
Author(s):  
Melissa Moey ◽  
Venkatesh Rajapurohitam ◽  
Asad Zeidan ◽  
Morris Karmazyn
Keyword(s):  
Protein Kinase ◽  
Coiled Coil ◽  
Mitogen Activated Protein Kinase ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Pathway Activation ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

scholarly journals Two Ras Pathways in Fission Yeast Are Differentially Regulated by Two Ras Guanine Nucleotide Exchange Factors

2002 ◽  
Vol 22 (13) ◽  
pp. 4598-4606 ◽  
Author(s):  
Piyi Papadaki ◽  
Véronique Pizon ◽  
Brian Onken ◽  
Eric C. Chang
Keyword(s):  
Mitogen Activated Protein Kinase ◽  
Critical Element ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Signaling Specificity ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Mitogen Activated Protein ◽  
Kinase Cascade ◽  
Synthetically Lethal

ABSTRACT How a given Ras prreotein coordinates multiple signaling inputs and outputs is a fundamental issue of signaling specificity. Schizosaccharomyces pombe contains one Ras, Ras1, that has two distinct outputs. Ras1 activates Scd1, a presumptive guanine nucleotide exchange factor (GEF) for Cdc42, to control morphogenesis and chromosome segregation, and Byr2, a component of a mitogen-activated protein kinase cascade, to control mating. So far there is only one established Ras1 GEF, Ste6. Paradoxically, ste6 null (ste6Δ) mutants are sterile but normal in cell morphology. This suggests that Ste6 specifically activates the Ras1-Byr2 pathway and that there is another GEF capable of activating the Scd1 pathway. We thereby characterized a potential GEF, Efc25. Genetic data place Efc25 upstream of the Ras1-Scd1, but not the Ras1-Byr2, pathway. Like ras1Δ and scd1Δ, efc25Δ is synthetically lethal with a deletion in tea1, a critical element for cell polarity control. Using truncated proteins, we showed that the C-terminal GEF domain of Efc25 is essential for function and regulated by the N terminus. We conclude that Efc25 acts as a Ras1 GEF specific for the Scd1 pathway. While ste6 expression is induced during mating, efc25 expression is constitutive. Moreover, Efc25 overexpression renders cells hyperelongated and sterile; the latter can be rescued by activated Ras1. This suggests that Efc25 can recruit Ras1 to selectively activate Scd1 at the expense of Byr2. Reciprocally, Ste6 overexpression can block Scd1 activation. We propose that external signals can partly segregate two Ras1 pathways by modulating GEF expression and that GEFs can influence how Ras is coupled to specific effectors.

scholarly journals TcR and TcR-CD28 Engagement of Protein Kinase B (PKB/AKT) and Glycogen Synthase Kinase-3 (GSK-3) Operates Independently of Guanine Nucleotide Exchange Factor VAV-1

2006 ◽  
Vol 281 (43) ◽  
pp. 32385-32394 ◽  
Author(s):  
Joanne E. Wood ◽  
Helga Schneider ◽  
Christopher E. Rudd
Keyword(s):  
T Cells ◽  
Protein Kinase ◽  
Glycogen Synthase ◽  
Protein Kinase B ◽  
Guanine Nucleotide Exchange Factor ◽  
Glycogen Synthase Kinase 3 ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor

TcRζ/CD3 and TcRζ/CD3-CD28 signaling requires the guanine nucleotide exchange factor (GEF) Vav-1 as well as the activation of phosphatidylinositol 3-kinase, protein kinase B (PKB/AKT), and its inactivation of glycogen synthase kinase-3 (GSK-3). Whether these two pathways are connected or operate independently of each other in T-cells has been unclear. Here, we report that anti-CD3 and anti-CD3/CD28 can induce PKB and GSK-3α phosphorylation in the Vav-1–/– Jurkat cell line J. Vav.1 and in primary CD4-positive Vav-1–/– T-cells. Reduced GSK-3α phosphorylation was observed in Vav-1,2,3–/– T-cells together with a complete loss of FOXO1 phosphorylation. Furthermore, PKB and GSK-3 phosphorylation was unperturbed in the presence of GEF-inactive Vav-1 that inhibited interleukin-2 gene activation and a form of Src homology 2 domain-containing lymphocytic protein of 76-kDa (SLP-76) that is defective in binding to Vav-1. The pathway also was intact under conditions of c-Jun N-terminal kinase (JNK) inhibition and disruption of the actin cytoskeleton by cytochalasin D. Both events are down-stream targets of Vav-1. Overall, our findings indicate that the TcR and TcR-CD28 driven PKB-GSK-3 pathway can operate independently of Vav-1 in T-cells.

N-terminal targeting of guanine nucleotide exchange factors (GEF) for ADP ribosylation factors (ARF) to the Golgi

2000 ◽  
Vol 113 (11) ◽  
pp. 1883-1889 ◽  
Author(s):  
S.Y. Lee ◽  
B. Pohajdak
Keyword(s):  
Coiled Coil ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Ph Domain ◽  
Adp Ribosylation ◽  
Guanine Nucleotide Exchange ◽  
Coiled Coil Domain ◽  
Nucleotide Exchange Factor ◽  
N Terminus ◽  
Point Mutagenesis

B2-1 (cytohesin-1) is a member of a group of proteins (including ARNO and ARNO3) that are all of similar size and domain composition. The three proteins contain an N-terminal coiled-coil domain, followed by a Sec7 and a pleckstrin homology (PH) domain. While it is well established that the Sec7 domain functions as a guanine nucleotide exchange factor (GEF) for ADP-ribosylation factors (ARFs) and the PH domain anchors the proteins to membrane phosphoinositols, the function of the N-terminal domain is unknown. Here we show that the N terminus of B2-1 (residues 1–54) is necessary and sufficient to target the protein to the Golgi. The Sec7+PH domains of B2-1 (residues 55–398) are not sufficient for Golgi localization. Further deletion analysis and point mutagenesis indicate that the coiled-coil domain within the N terminus is responsible for Golgi targeting. Furthermore, ARNO and ARNO3 N termini also have the same capability of targeting to the Golgi. We conclude that the N-terminal, (α)-helical, coiled-coil domain is used to target this family of proteins to the Golgi complex.

scholarly journals Cleavage of the signaling mucin Msb2 by the aspartyl protease Yps1 is required for MAPK activation in yeast

2008 ◽  
Vol 181 (7) ◽  
pp. 1073-1081 ◽  
Author(s):  
Nadia Vadaie ◽  
Heather Dionne ◽  
Darowan S. Akajagbor ◽  
Seth R. Nickerson ◽  
Damian J. Krysan ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Active Form ◽  
Cell Polarization ◽  
Mitogen Activated Protein Kinase ◽  
Aspartyl Protease ◽  
Nucleotide Exchange ◽  
Mapk Activation ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Mitogen Activated Protein

Signaling mucins are cell adhesion molecules that activate RAS/RHO guanosine triphosphatases and their effector mitogen-activated protein kinase (MAPK) pathways. We found that the Saccharomyces cerevisiae mucin Msb2p, which functions at the head of the Cdc42p-dependent MAPK pathway that controls filamentous growth, is processed into secreted and cell-associated forms. Cleavage of the extracellular inhibitory domain of Msb2p by the aspartyl protease Yps1p generated the active form of the protein by a mechanism incorporating cellular nutritional status. Activated Msb2p functioned through the tetraspan protein Sho1p to induce MAPK activation as well as cell polarization, which involved the Cdc42p guanine nucleotide exchange factor Cdc24p. We postulate that cleavage-dependent activation is a general feature of signaling mucins, which brings to light a novel regulatory aspect of this class of signaling adhesion molecule.

Sign in / Sign up

Export Citation Format

Share Document