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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.

Use of elicitor sets to characterize cellular signal transduction networks

Narayanan, Arthi 26 September 2003 (has links)
Intracellular signaling cascades can no longer be viewed as linear pathways that relay and amplify information. Often, components of different pathways interact, resulting in signaling networks. The interactions of different pathways and the dynamic modulation of the activities of the components within signaling pathways can create a multitude of biological outputs. The cell appears to use these pathways as a way of integrating multiple inputs to shape a uniquely defined output. These outputs allow the cell to respond to and adapt to an ever-changing environment. Understanding how biological systems receive, process and respond to complex data inputs has important implications for the design and utilization of sensors for a variety of applications, including toxicology, pharmacology, medical diagnostics, and environmental monitoring. This study uses the elicitor sets method, which is an experimental framework designed to monitor information flows through signal transduction pathways. The elicitor set approach has been used to derive mechanistic interpretations from the action of Phenylmethylsulfonyl Fluoride (PMSF), a serine protease inhibitor and nerve agent analog. The elicitor panel comprises of signal transduction network effectors namely forskolin, clonidine, cirazoline and H89, each of which targets the signaling pathway at known specific points. The elicitor set experiments enable compartmentalization of the cAMP signaling pathway, examining the role played by each segment and identifying possible cross-talk mechanisms. Our experiments substantiate that selection of adenyl cyclase as the reference node and 10 [mu]M forskolin as the primary elicitor, segments the upper portion of the G-Protein Coupled Receptor (GPCR) pathway associated with the G[sub q] and G[sub i] proteins. Application of the secondary elicitors, 100 nM clonidine (a2-adrenergic receptor agonist), 1 pM and 100 pM cirazoline (al-adrenergic receptor agonists), and 1 [mu]M and 100 [mu]M H-89 (PKA inhibitor) fortifies the decoupling, as the system is unresponsive to clonidine and cirazoline in the presence of forskolin, while continuing to respond to H-89. Exposure of the cells to 1 mM PMSF subsequent to forskolin addition restricted the quantifiable impact of PMSF to regions of the signaling pathways below adenyl cyclase. Triggering the system by use of secondary elicitors augmented the information resolution which is reinforced by the increased sensitivity of cells to 100 [mu]M H-89 that acts at an important checkpoint below adenyl cyclase. / Graduation date: 2004

Functional segregation of the highly conserved basic motifs within the third endoloop of the human secretin receptor /

Chan, Yuen-yee, Kathy, January 2001 (has links)
Thesis (Ph. D.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 85-112).

The involvement of Lyn and the SH2-domain-containing inositol 5'-phosphatase 1 (SHIP1) in the negative regulation of M-CSF-induced cellular signaling events

Baran, Christopher, Phillip, January 2003 (has links)
Thesis (Ph. D.)--Ohio State University, 2003. / Title from first page of PDF file. Document formatted into pages; contains x, 92 p.: ill. Includes abstract and vita. Advisor: Clay B. Marsh, Dept. of Veterinary Biosciences. Includes bibliographical references (p. 84-92).

PDZD2, a candidate for brachydactyly type A1, encodes a secreted protein that negatively modulates hedgehog signaling

Tsui, Michelle Grace, 徐善婷 January 2014 (has links)
Hedgehog (Hh) is an important morphogen that dictates tissue patterning during embryonic development. Recent studies showed that mutation in Indian Hedgehog(IHH)resulted in Brachydactyly type A1(BDA1);however, the disease pathogenesis in patients without IHH mutation remained unknown. PDZD2 is a multi-PDZ domain-containing protein of unknown function in early development. Human PDZD2 is mapped to chromosome 5p13.2, which co-localizes with the disease-associated gene in a family of BDA1 patients, suggesting involvement of PDZD2 in limb development. In situ hybridization revealed that Pdzd2 was expressed in the distal mesenchyme partially overlapping with Shh expressionin mouse limb bud. During digit patterning, Pdzd2 was expressed in the interzone regions that flanked the Ihh/Gli1-expressing phalanx condensation. Moreover,Pdzd2 was expressed in the paraxial mesoderm adjacent to the differentiating neural tube. Pdzd2expression in various Hh-active tissues in mouse and chicken suggested an evolutionary conserved role of PDZD2 in modulating general Hh signaling during early development. Interestingly, PDZD2 protein was detected at the neural tube away from its site of synthesis, suggesting a non-cell autonomous role of PDZD2 possibly via its secreted form, sPDZD2. Functional studies showed that overexpression of sPDZD2 in the chicken neural tube leads to down-regulation ofNKX2.2andOLIG2expression.sPDZD2 was shown to counteract the ectopic NKX2.2 expression induced by long-range signaling of ectopic HH. Consistently, sPDZD2exhibited an inhibitory effect on SHH-induced reporter activity in a Gli-luciferase cell line. For in vivo analysis, a transgenic mouse line carrying a floxed Pdzd2 allele (Pdzd2fl) was generated to ablate Pdzd2 expression.Pdzd2+/fl mice were crossed with Protamine-cre to generate the null allele (Pdzd2-). However, heterozygous intercross yielded no homozygous mutant as early as E9.5, suggesting early embryonic lethality. Thus, conditional Pdzd2 knock-out in the limb was pursuedusingPrx1-cre.However, no significant perturbation of Hh signaling was observed in Pdzd2fl/fl:Prx1-cre limb buds, which might be due to incomplete knock-out of Pdzd2, or functional redundancy among Hh modulators. To study the relevance of Pdzd2in the development of BDA1, Pdzd2-/fl mouse was crossed with the BDA1 mouseIhhE95K/E95Kto study the effect of reducing Pdzd2expression under defective Hh signaling. Preliminary analysis of the Pdzd2+/-, Ihh+/E95K compound mutants showed more severe phenotypes comparing with IhhE95K/E95K. These included delayed limb development and further diffusion ofGli1expression in the digits, suggestive of a direct involvement of Pdzd2in BDA1. It was speculated that Pdzd2negatively modulated Ihh signaling and restricted Hh signals from entering the interzone, which was required for normal digit patterning. Depletion of Pdzd2might result in an expansion of Ihh signaling into the interzone, leading to the BDA1phenotypessimilar to the current BDA1 disease model proposed forIhhE95Kmutation. Taken together, my study revealed the novel expression of Pdzd2in close proximity to multiple Hh-active tissues during early development and provided the first evidence that PDZD2/sPDZD2 is a negative modulator of general Hh signaling. These data strongly supported PDZD2as a disease-associated locus in the family of BDA1 patients that do not carry IHHmutations. / published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

Case studies on the aspects of molecular signaling: binding forces, signal generation, and a mature receptor

Houk, Ronald James Travis 28 August 2008 (has links)
Not available / text

Case studies on the aspects of molecular signaling : binding forces, signal generation, and a mature receptor

Houk, Ronald James Travis, 1979- 23 August 2011 (has links)
Not available / text

Regulation of phorbol ester-induced Ras/Raf/Erk signaling pathway in EL4 cells

Han, Shujie, January 2008 (has links) (PDF)
Thesis (Ph. D.)--Washington State University, August 2008. / Includes bibliographical references (p. 88-101).

The involvement of JAK2/STAT2/STAT3 in myogenic differentiation /

Wang, Kepeng. January 2008 (has links)
Thesis (Ph.D.)--Hong Kong University of Science and Technology, 2008. / Includes bibliographical references (leaves 73-96). Also available in electronic version.

RET/PTC1-mediated phosphotyrosine signaling pathways involved in thyroid cell transformation

Venkateswaran, Anjli, January 2004 (has links)
Thesis (Ph. D.)--Ohio State University, 2004. / Title from first page of PDF file. Document formatted into pages; contains xvi, 157 p.; also includes graphics (some col.) Includes bibliographical references (p. 146-157).

The photochemical and structural basis of phototropin-mediated signal transduction /

Crosson, Sean David. January 2002 (has links)
Thesis (Ph. D.)--University of Chicago, Dept. of Biochemistry and Molecular Biology, December 2002. / Includes bibliographical references. Also available on the Internet.

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