scholarly journals Molecular Characterization of the Dominant-Negative Role of Cancer-Associated PTEN: Sometimes, Null is Better

2014 ◽  
Vol 4 ◽  
Author(s):  
Saverio Marchi ◽  
Paolo Pinton
Keyword(s):  
Molecular Characterization ◽  
Dominant Negative ◽  
Negative Role

PHYSIOLOGIC AND MOLECULAR CHARACTERIZATION OF THE ROLE OF NITRIC OXIDE IN HEMORRHAGIC SHOCK

Shock ◽  
1997 ◽  
Vol 7 (3) ◽  
pp. 157-163 ◽  
Author(s):  
Edward Kelly ◽  
Nishit S. Shah ◽  
Nathan N. Morgan ◽  
Simon C. Watkins ◽  
Andrew B. Peitzman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Hemorrhagic Shock ◽  
Molecular Characterization

The function and regulation of cut expression on the wing margin of Drosophila: Notch, Wingless and a dominant negative role for Delta and Serrate

Development ◽  
1997 ◽  
Vol 124 (8) ◽  
pp. 1485-1495 ◽  
Author(s):  
C.A. Micchelli ◽  
E.J. Rulifson ◽  
S.S. Blair
Keyword(s):  
Gene Expression ◽  
Ventral Side ◽  
Dominant Negative ◽  
Specific Marker ◽  
Wing Margin ◽  
Dynamic Feedback ◽  
Compartment Boundary ◽  
Wingless Signaling ◽  
Negative Role

We have investigated the role of the Notch and Wingless signaling pathways in the maintenance of wing margin identity through the study of cut, a homeobox-containing transcription factor and a late-arising margin-specific marker. By late third instar, a tripartite domain of gene expression can be identified about the dorsoventral compartment boundary, which marks the presumptive wing margin. A central domain of cut- and wingless-expressing cells are flanked on the dorsal and ventral side by domains of cells expressing elevated levels of the Notch ligands Delta and Serrate. We show first that cut acts to maintain margin wingless expression, providing a potential explanation of the cut mutant phenotype. Next, we examined the regulation of cut expression. Our results indicate that Notch, but not Wingless signaling, is autonomously required for cut expression. Rather, Wingless is required indirectly for cut expression; our results suggest this requirement is due to the regulation by wingless of Delta and Serrate expression in cells flanking the cut and wingless expression domains. Finally, we show that Delta and Serrate play a dual role in the regulation of cut and wingless expression. Normal, high levels of Delta and Serrate can trigger cut and wingless expression in adjacent cells lacking Delta and Serrate. However, high levels of Delta and Serrate also act in a dominant negative fashion, since cells expressing such levels cannot themselves express cut or wingless. We propose that the boundary of Notch ligand along the normal margin plays a similar role as part of a dynamic feedback loop that maintains the tripartite pattern of margin gene expression.

scholarly journals Molecular insights into regulation of JAK2 in myeloproliferative neoplasms

Blood ◽  
2015 ◽  
Vol 125 (22) ◽  
pp. 3388-3392 ◽  
Author(s):  
Olli Silvennoinen ◽  
Stevan R. Hubbard
Keyword(s):  
Molecular Characterization ◽  
Human Disease ◽  
Molecular Mechanisms ◽  
Myeloproliferative Neoplasms ◽  
Critical Role ◽  
Hematologic Malignancies ◽  
Janus Kinase ◽  
Constitutive Activation

Abstract The critical role of Janus kinase-2 (JAK2) in regulation of myelopoiesis was established 2 decades ago, but identification of mutations in the pseudokinase domain of JAK2 in myeloproliferative neoplasms (MPNs) and in other hematologic malignancies highlighted the role of JAK2 in human disease. These findings have revolutionized the diagnostics of MPNs and led to development of novel JAK2 therapeutics. However, the molecular mechanisms by which mutations in the pseudokinase domain lead to hyperactivation of JAK2 and clinical disease have been unclear. Here, we describe recent advances in the molecular characterization of the JAK2 pseudokinase domain and how pathogenic mutations lead to constitutive activation of JAK2.

scholarly journals Molecular characterization of MRSA isolates bracketing the current EUCAST ceftaroline-susceptible breakpoint forStaphylococcus aureus: the role of PBP2a in the activity of ceftaroline

2015 ◽  
Vol 70 (9) ◽  
pp. 2488-2498 ◽  
Author(s):  
Sushmita D. Lahiri ◽  
Robert E. McLaughlin ◽  
James D. Whiteaker ◽  
Jane E. Ambler ◽  
Richard A. Alm
Keyword(s):  
Molecular Characterization

scholarly journals Genetic evidence for signal transduction within the Bacillus subtilis GerA germinant receptor

2021 ◽  
Author(s):  
Jeremy D. Amon ◽  
Lior Artzi ◽  
David Z. Rudner
Keyword(s):  
Signal Transduction ◽  
Bacillus Subtilis ◽  
Signal Transduction Pathway ◽  
Dominant Negative ◽  
Transduction Pathway ◽  
Sense And Respond ◽  
Enrichment Strategy ◽  
Functional Receptor

Bacterial spores can rapidly exit dormancy through the process of germination. This process begins with the activation of nutrient receptors embedded in the spore membrane. The prototypical germinant receptor in Bacillus subtilis responds to L-alanine and is thought to be a complex of proteins encoded by the genes in the gerA operon: gerAA , gerAB , and gerAC . The GerAB subunit has recently been shown to function as the nutrient sensor, but beyond contributing to complex stability, no additional functions have been attributed to the other two subunits. Here, we investigate the role of GerAA. We resurrect a previously characterized allele of gerA (termed gerA* ) that carries a mutation in gerAA and show it constitutively activates germination even in the presence of a wild-type copy of gerA . Using an enrichment strategy to screen for suppressors of gerA* , we identified mutations in all three gerA genes that restore a functional receptor. Characterization of two distinct gerAB suppressors revealed that one ( gerAB[E105K]) reduces the GerA complex's ability to respond to L-alanine, while another ( gerAB[F259S] ) disrupts the germinant signal downstream of L-alanine recognition. These data argue against models in which GerAA is directly or indirectly involved in germinant sensing. Rather, our data suggest that GerAA is responsible for transducing the nutrient signal sensed by GerAB. While the steps downstream of gerAA have yet to be uncovered, these results validate the use of a dominant-negative genetic approach in elucidating the gerA signal transduction pathway. Importance Endospore formers are a broad group of bacteria that can enter dormancy upon starvation and exit dormancy upon sensing the return of nutrients. How dormant spores sense and respond to these nutrients is poorly understood. Here, we identify a key step in the signal transduction pathway that is activated after spores detect the amino acid L-alanine. We present a model that provides a more complete picture of this process that is critical for allowing dormant spores to germinate and resume growth.

scholarly journals Genetic evidence for signal transduction within the Bacillus subtilis GerA germinant receptor

2021 ◽  
Author(s):  
Jeremy D. Amon ◽  
Lior Artzi ◽  
David Z. Rudner
Keyword(s):  
Signal Transduction ◽  
Bacillus Subtilis ◽  
Signal Transduction Pathway ◽  
Dominant Negative ◽  
Bacterial Spores ◽  
Wild Type ◽  
Enrichment Strategy ◽  
Functional Receptor

Bacterial spores can rapidly exit dormancy through the process of germination. This process begins with the activation of nutrient receptors embedded in the spore membrane. The prototypical germinant receptor in Bacillus subtilis responds to L-alanine and is thought to be a complex of proteins encoded by the genes in the gerA operon: gerAA, gerAB, and gerAC. The GerAB subunit has recently been shown to function as the nutrient sensor, but beyond contributing to complex stability, no additional functions have been attributed to the other two subunits. Here, we investigate the role of GerAA. We resurrect a previously characterized allele of gerA (termed gerA*) that carries a mutation in gerAA and show it constitutively activates germination even in the presence of a wild-type copy of gerA. Using an enrichment strategy to screen for suppressors of gerA*, we identified mutations in all three gerA genes that restore a functional receptor. Characterization of two distinct gerAB suppressors revealed that one (gerAB-E105K) reduces the GerA complex's ability to respond to L-alanine, while another (gerAB-F259S) disrupts the germinant signal downstream of L-alanine recognition. These data argue against models in which GerAA is directly or indirectly involved in germinant sensing. Rather, our data suggest that GerAA is responsible for transducing the nutrient signal sensed by GerAB. While the steps downstream of gerAA have yet to be uncovered, these results validate the use of a dominant-negative genetic approach in elucidating the gerA signal transduction pathway.

scholarly journals Molecular characterization of Kv2.1 channels in sheep vasculature: Role of Kv channels in regulating vascular tone

2006 ◽  
Vol 20 (5) ◽  
Author(s):  
K Dinesh ◽  
S Hirenallur ◽  
Avinash G Telang ◽  
Santhosh K Mishra
Keyword(s):  
Molecular Characterization ◽  
Vascular Tone ◽  
Kv Channels
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