Shape and Quantitative Analysis of Factor #4 (Filopodia) and Factor #7 (Massive Protrusions) in Tumorigenic Cells
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ndltd-OhioLink-oai-etd.ohiolink.edu-bgsu12078598572021-08-03T05:28:38Z Shape and Quantitative Analysis of Factor #4 (Filopodia) and Factor #7 (Massive Protrusions) in Tumorigenic Cells Malwade, Santosh Ramkrishna Biology filopodia massive protrusions Nck-alpha Kinase inhibitory domain Focal contact <p>After activation by guanine triphosphatases (GTPases) like Rac and cell division control protein (Cdc42), the p21-activated kinase (PAK) unfolds and binds tightly with SH3 domain of partner PAK-interacting exchange factor (PIX). PIX binds to G protein coupled receptor kinase interacting protein (GIT1) which binds to paxillin. Paxillin binds to focal adhesion kinase (FAK). The N-terminal region of PAK binds with Nck-alpha through its SH3 domain and Nck-alpha binds to FAK. This chain of five proteins is located at the focal contact site and believed to be important for production of filopodia and membrane protrusion. At the regulatory level, the mechanism is not known but could be clarified by further work. </p><p> I studied the role of PAK in the formation of these two protrusions, by supplying PAK kinase inhibitor, PAK83-149, in the presence or absence of Nck-alpha. These two constructs were found to have an effect statistically distinguishable from control in previous experiments. Filopodia and larger membrane protrusions were affected differently by Nck-alpha alone and PAK83-149 alone. The large protrusions were more prevalent with Nck-alpha alone and unaffected by PAK83-149. Expression of both constructs together was required to affect the filopodia. When the cells were treated with tyrosine phosphatase inhibitor, phenylarsine oxide (PAO), the results of Nck-alpha and PAK83-149 expression were different. PAK83-149 now showed a significant effect on massive protrusion formation which was statistically distinguishable from all other groups. None of the treatments any longer promoted filopodia formation. Surprisingly the effect of Nck-alpha in all treated samples was removed by PAO. Maybe the Nck-alpha alone affects the protrusions by binding PAK molecules to sites on receptors such as phosphorylated focal adhesion kinase (FAK), or transmembrane growth factor receptors. The reversal of this effect by PAO is a novel effect.</p> 2008-07-29 English text Bowling Green State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1207859857 http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1207859857 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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English |
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Biology filopodia massive protrusions Nck-alpha Kinase inhibitory domain Focal contact |
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Biology filopodia massive protrusions Nck-alpha Kinase inhibitory domain Focal contact Malwade, Santosh Ramkrishna Shape and Quantitative Analysis of Factor #4 (Filopodia) and Factor #7 (Massive Protrusions) in Tumorigenic Cells |
author |
Malwade, Santosh Ramkrishna |
author_facet |
Malwade, Santosh Ramkrishna |
author_sort |
Malwade, Santosh Ramkrishna |
title |
Shape and Quantitative Analysis of Factor #4 (Filopodia) and Factor #7 (Massive Protrusions) in Tumorigenic Cells |
title_short |
Shape and Quantitative Analysis of Factor #4 (Filopodia) and Factor #7 (Massive Protrusions) in Tumorigenic Cells |
title_full |
Shape and Quantitative Analysis of Factor #4 (Filopodia) and Factor #7 (Massive Protrusions) in Tumorigenic Cells |
title_fullStr |
Shape and Quantitative Analysis of Factor #4 (Filopodia) and Factor #7 (Massive Protrusions) in Tumorigenic Cells |
title_full_unstemmed |
Shape and Quantitative Analysis of Factor #4 (Filopodia) and Factor #7 (Massive Protrusions) in Tumorigenic Cells |
title_sort |
shape and quantitative analysis of factor #4 (filopodia) and factor #7 (massive protrusions) in tumorigenic cells |
publisher |
Bowling Green State University / OhioLINK |
publishDate |
2008 |
url |
http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1207859857 |
work_keys_str_mv |
AT malwadesantoshramkrishna shapeandquantitativeanalysisoffactor4filopodiaandfactor7massiveprotrusionsintumorigeniccells |
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