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[ subject:"Biology, Neurobiology." ]
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Modulation of growth factor-induced ...
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Leugers, Chad Jeremy.
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Modulation of growth factor-induced ERK signaling by the microtubule associated protein tau.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
Modulation of growth factor-induced ERK signaling by the microtubule associated protein tau./
作者:
Leugers, Chad Jeremy.
面頁冊數:
136 p.
附註:
Source: Dissertation Abstracts International, Volume: 71-07, Section: B, page: 4076.
Contained By:
Dissertation Abstracts International71-07B.
標題:
Biology, Neuroscience. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3409500
ISBN:
9781124070667
Modulation of growth factor-induced ERK signaling by the microtubule associated protein tau.
Leugers, Chad Jeremy.
Modulation of growth factor-induced ERK signaling by the microtubule associated protein tau.
- 136 p.
Source: Dissertation Abstracts International, Volume: 71-07, Section: B, page: 4076.
Thesis (Ph.D.)--The University of Iowa, 2010.
The microtubule-associated protein tau is known for its ability to bind to and stabilize microtubules and for its ability to nucleate microtubule assembly. In neurodegenerative tauopathies such as Alzheimer's disease, tau becomes hyperphosphorylated and loses the capacity for microtubule binding, possibly contributing to microtubule destabilization and axonal degeneration. However, evidence now indicates that soluble forms of hyperphosphorylated tau might have a toxic gain of function linked to abnormal signal transduction and cell cycle events in normally post-mitotic neurons. In support of this hypothesis, tau has been found to associate with numerous signaling proteins such as tyrosine kinases, adaptor proteins, and scaffold proteins. During early brain development, fetal tau is also more phosphorylated than tau in the adult brain and weakly binds microtubules, suggesting tau has functions in addition to microtubule stabilization.
ISBN: 9781124070667Subjects--Topical Terms:
1017680
Biology, Neuroscience.
Modulation of growth factor-induced ERK signaling by the microtubule associated protein tau.
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The microtubule-associated protein tau is known for its ability to bind to and stabilize microtubules and for its ability to nucleate microtubule assembly. In neurodegenerative tauopathies such as Alzheimer's disease, tau becomes hyperphosphorylated and loses the capacity for microtubule binding, possibly contributing to microtubule destabilization and axonal degeneration. However, evidence now indicates that soluble forms of hyperphosphorylated tau might have a toxic gain of function linked to abnormal signal transduction and cell cycle events in normally post-mitotic neurons. In support of this hypothesis, tau has been found to associate with numerous signaling proteins such as tyrosine kinases, adaptor proteins, and scaffold proteins. During early brain development, fetal tau is also more phosphorylated than tau in the adult brain and weakly binds microtubules, suggesting tau has functions in addition to microtubule stabilization.
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The aim of this dissertation research is to investigate the possible role of tau in neuronal signaling, using tau-expressing and tau-depleted cell lines. Here, we provide evidence that during growth factor stimulation of neuronal cells, tau functions in advance of the neurite elongation stage. Tau is required for neurite initiation in a manner that does not require its microtubule binding function, and in addition, tau potentiates AP-1 transcription factor activation in response to nerve growth factor (NGF). The effect of tau on AP-1 activation is mediated through the enhanced activation of extracellular signal-regulated kinase (ERK), in response to both NGF and epidermal growth factor (EGF). We show that phosphorylation of tau at Thr231 also occurs in response to NGF and is required for tau to impact on ERK signaling, whereas the ability of tau to bind to microtubules is not required. Together, these findings indicate a new functional role for tau in neuronal signal transduction and have implications for tau function during early brain development and in neurodegenerative disease.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3409500
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