Mesoderm formation in Xenopus ectodermal explants overexpressing Xwnt8: evidence for a cooperating signal reaching the animal pole by gastrulation

Development ◽  
1993 ◽  
Vol 118 (4) ◽  
pp. 1335-1342 ◽  
Author(s):  
S.Y. Sokol
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathways ◽  
Blastula Stage ◽  
Animal Pole ◽  
Dorsoventral Axis ◽  
Mesoderm Formation ◽  
Dependent Signal ◽  
Combined Action ◽  
Early Gastrula

It is demonstrated here that the ability of injected Xwnt8 RNA to trigger mesoderm formation in Xenopus presumptive ectoderm (animal caps) depends on the time of explantation. Animal caps isolated from Xwnt8 injected embryos at the late blastula/early gastrula stages differentiate mesodermal tissues whereas caps isolated from early blastula do not. This finding suggests that an endogenous signal reaches the animal cap by the late blastula stage and cooperates with Xwnt8 to induce mesoderm. Similarly, late animal caps isolated at st. 10 from lithium-treated embryos, but not those from control embryos, elongate and express muscle-specific actin transcripts. In addition, the data presented suggests that the cooperating signal is distributed homogeneously with respect to the future dorsoventral axis and may require FGF- and activin-dependent signal transduction pathways. These observations support a model in which mesoderm is induced in vivo by a combined action of several different signals.

Control of Mammary Differentiation by Ras-Dependent Signal Transduction Pathways

2002 ◽  
Author(s):  
Mary L. Cutler ◽  
Mari G. Cerrito ◽  
Treas Chopp ◽  
Weihan Wang
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathways ◽  
Dependent Signal

Preclinical Analysis of the Combined Activity of SGN-40, Anti-CD40 Monoclonal Antibody, with Rituximab in Non-Hodgkin Lymphoma.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1583-1583 ◽  
Author(s):  
Timothy S. Lewis ◽  
Renee S. McCormick ◽  
Julie A. McEarchern ◽  
Kim Kissler ◽  
Ivan J. Stone ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Monoclonal Antibody ◽  
Family Member ◽  
Cell Lines ◽  
Tumor Response ◽  
Effector Function ◽  
Signal Transduction Pathways ◽  
Non Hodgkin Lymphoma ◽  
Function Activity

Abstract SGN-40 is a humanized monoclonal antibody against CD40, a TNF receptor family member expressed in non-Hodgkin lymphoma (NHL), multiple myeloma, and several carcinomas. SGN-40 is cytotoxic to NHL cell lines via activation of proapoptotic signal transduction pathways and mediates antibody dependent cellular cytotoxicity (ADCC) effector function activity. In this study we examined the anti-tumor activity of SGN-40 in combination with the anti-CD20 antibody, rituximab, in lymphoma cell line models. Cell proliferation data (3H-thymidine incorporation assay) was generated for SGN-40 and rituximab alone and in combination for three NHL cell lines (Ramos, RL, and SU-DHL-4) and combination index (CI) analyses performed. SGN-40 was reproducibly synergistic with rituximab in Ramos cells and additive in the RL and SU-DHL-4 cell lines in this assay. This suggested that different anti-proliferative signaling events are activated by these antibodies, which produce a greater anti-tumor effect when combined. To better understand the combined activity of SGN-40 and rituximab, the signal transduction pathways activated by each antibody were examined. In Ramos cells SGN-40 signaling caused the degradation of pro-survival BCL-6 oncoprotein and upregulation of TAp63α, a proapoptic p53 family member, while only BCL-6 degradation was triggered in the RL and SU-DHL-4 cell lines. In contrast, rituximab signaling degraded BCL-6 protein in only one cell line (SU-DHL-4), and did not upregulate TAp63α expression in any of the cell lines examined. To further define the combined activity of SGN-40 with rituximab the effector function activity of both antibodies were examined in vitro. ADCC assays in the WIL2-S and Raji cell lines both showed a greater percent cell lysis in the presence of both SGN-40 and rituximab compared to either drug alone. Next, the SGN-40 and rituximab were tested in subcutaneous mouse models of NHL to evaluate this combination in vivo. In a Ramos model, SGN-40 and rituximab (dosed at 4.0mg/kg, q4dx4, ip) had significantly greater anti-tumor response when combined compared to the equivalent dose of either antibody alone. The anti-tumor response achieved with dual dosing of SGN-40 and rituximab was greater than the response expected if the combination was additive. Our data suggests that the improved efficacy of SGN-40, rituximab combination therapy in vivo is due to distinct apoptotic signaling pathways activated by these two antibodies in addition to augmented effector function activity. The combination of SGN-40 and rituximab is currently being studied in clinical trials of NHL.

scholarly journals Matrix nanotopography as a regulator of cell function

2012 ◽  
Vol 197 (3) ◽  
pp. 351-360 ◽  
Author(s):  
Deok-Ho Kim ◽  
Paolo P. Provenzano ◽  
Chris L. Smith ◽  
Andre Levchenko
Keyword(s):  
Signal Transduction ◽  
Cell Function ◽  
Control Cell ◽  
Signal Transduction Pathways ◽  
Cell Behavior ◽  
Powerful Means ◽  
Cell Processes ◽  
Chemical Factors ◽  
Physical Interactions

The architecture of the extracellular matrix (ECM) directs cell behavior by providing spatial and mechanical cues to which cells respond. In addition to soluble chemical factors, physical interactions between the cell and ECM regulate primary cell processes, including differentiation, migration, and proliferation. Advances in microtechnology and, more recently, nanotechnology provide a powerful means to study the influence of the ECM on cell behavior. By recapitulating local architectures that cells encounter in vivo, we can elucidate and dissect the fundamental signal transduction pathways that control cell behavior in critical developmental, physiological, and pathological processes.

scholarly journals Transcriptional Regulators Cph1p and Efg1p Mediate Activation of the Candida albicans Virulence Gene SAP5 during Infection

2002 ◽  
Vol 70 (2) ◽  
pp. 921-927 ◽  
Author(s):  
Peter Staib ◽  
Marianne Kretschmar ◽  
Thomas Nichterlein ◽  
Herbert Hof ◽  
Joachim Morschhäuser
Keyword(s):  
Signal Transduction ◽  
Candida Albicans ◽  
Genetic Recombination ◽  
Hyphal Growth ◽  
Transcriptional Regulators ◽  
Infected Tissue ◽  
Mitogen Activated Protein Kinase ◽  
Signal Transduction Pathways ◽  
Aspartic Proteinases

ABSTRACT The opportunistic fungal pathogen Candida albicans can cause superficial as well as systemic infections. Successful adaptation to the different host niches encountered during infection requires coordinated expression of various virulence traits, including the switch between yeast and hyphal growth forms and secretion of aspartic proteinases. Using an in vivo expression technology that is based on genetic recombination as a reporter of gene activation during experimental candidiasis in mice, we investigated whether two signal transduction pathways controlling hyphal growth, a mitogen-activated protein kinase cascade ending in the transcriptional activator Cph1p and a cyclic AMP-dependent regulatory pathway that involves the transcription factor Efg1p, also control expression of the SAP5 gene, which encodes one of the secreted aspartic proteinases and is induced by host signals soon after infection. Our results show that both transcriptional regulators are important for SAP5 activation in vivo. SAP5 expression was reduced in a cph1 mutant, although filamentous growth in infected tissue was not detectably impaired. SAP5 expression was also reduced, but not eliminated, in an efg1 null mutant, although this strain grew exclusively in the yeast form in infected tissue, demonstrating that in contrast to in vitro conditions, SAP5 activation during infection does not depend on growth of C. albicans in the hyphal form. In a cph1 efg1 double mutant, however, SAP5 expression in infected mice was almost completely eliminated, suggesting that the two signal transduction pathways are important for SAP5 expression in vivo. The avirulence of the cph1 efg1 mutant seemed to be caused not only by the inability to form hyphae but also by a loss of expression of additional virulence genes in the host.

scholarly journals The Core Dimerization Domains of Histidine Kinases Contain Recognition Specificity for the Cognate Response Regulator

2003 ◽  
Vol 185 (15) ◽  
pp. 4424-4431 ◽  
Author(s):  
Noriko Ohta ◽  
Austin Newton
Keyword(s):  
Signal Transduction ◽  
Caulobacter Crescentus ◽  
Response Regulator ◽  
Signal Transduction Pathways ◽  
Histidine Kinases ◽  
Helix Bundle ◽  
Recognition Specificity ◽  
Four Helix Bundle ◽  
Two Hybrid

ABSTRACT Histidine kinases DivJ and PleC initiate signal transduction pathways that regulate an early cell division cycle step and the gain of motility later in the Caulobacter crescentus cell cycle, respectively. The essential single-domain response regulator DivK functions downstream of these kinases to catalyze phosphotransfer from DivJ and PleC. We have used a yeast two-hybrid screen to investigate the molecular basis of DivJ and PleC interaction with DivK and to identify other His-Asp signal transduction proteins that interact with DivK. The only His-Asp proteins identified in the two-hybrid screen were five members of the histidine kinase superfamily. The finding that most of the kinase clones isolated correspond to either DivJ or PleC supports the previous conclusion that DivJ and PleC are cognate DivK kinases. A 66-amino-acid sequence common to all cloned DivJ and PleC fragments contains the conserved helix 1, helix 2 sequence that forms a four-helix bundle in histidine kinases required for dimerization, autophosphorylation and phosphotransfer. We present results that indicate that the four-helix bundle subdomain is not only necessary for binding of the response regulator but also sufficient for in vivo recognition specificity between DivK and its cognate histidine kinases. The other three kinases identified in this study correspond to DivL, an essential tyrosine kinase belonging to the same kinase subfamily as DivJ and PleC, and the two previously uncharacterized, soluble histidine kinases CckN and CckO. We discuss the significance of these results as they relate to kinase response regulator recognition specificity and the fidelity of phosphotransfer in signal transduction pathways.

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