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The Abl2 Non-Receptor Tyrosine Kinase and Cortactin Form Actin Waves that Promote Lamellipodia Formation

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서명/저자사항The Abl2 Non-Receptor Tyrosine Kinase and Cortactin Form Actin Waves that Promote Lamellipodia Formation.
개인저자Zhang, Ke.
단체저자명Yale University. Cell Biology in MD/PhD Program.
발행사항[S.l.]: Yale University., 2019.
발행사항Ann Arbor: ProQuest Dissertations & Theses, 2019.
형태사항152 p.
기본자료 저록Dissertations Abstracts International 81-03B.
Dissertation Abstract International
ISBN9781085790031
학위논문주기Thesis (Ph.D.)--Yale University, 2019.
일반주기 Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
Advisor: Koleske, Anthony J.
이용제한사항This item must not be sold to any third party vendors.This item must not be added to any third party search indexes.
요약Abl family non-receptor tyrosine kinases regulate dynamic changes in cell shape and migration through direct binding and phosphorylation of cytoskeleton-regulating proteins and cell surface receptors. Interactions of Abl2 with cortactin, an actin filament stabilizer and activator of the Arp2/3 complex, are critical for the stability of these dynamic actin-rich structures, but Abl2:cortactin-positive structures have not been characterized with high spatiotemporal precision in live cells. Using high speed two-color Total Internal Reflection Fluorescent (TIRF) microscopy, we demonstrate that Abl2 colocalizes with cortactin both at actively protruding actin waves on the ventral membrane and at the tips of lamellipodia in COS-7 cells. Here, I present work demonstrating that Abl2 and cortactin are recruited to actin waves through direct interactions with the cytoskeleton to promote the formation of transient Abl2:cortactin-positive actin waves and lamellipodia. Abl2 has C-terminal actin- and microtubule-binding domains that distinguish it from all other known non-receptor tyrosine kinases. These domains perform crucial kinase-independent functions at the cell periphery. How Abl2 balances its kinase activity with its C-terminal cytoskeleton interactions to properly localize to the cell periphery has not been fully addressed. In this thesis, I present a background on single particle microscopy to studying proteins at the cell membrane and present work using live cell TIRF microscopy to probe the roles of Abl2 domains for localization and mobility on the cell membrane.
일반주제명Cellular biology.
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