Journal ArticleDOI
Cdc42 regulates GSK-3beta and adenomatous polyposis coli to control cell polarity.
TLDR
It is shown, through the use of primary rat astrocytes in a cell migration assay, that Par6–PKCζ interacts directly with and regulates glycogen synthase kinase-3 β (GSK-3β) to promote polarization of the centrosome and to control the direction of cell protrusion.Abstract:
Cell polarity is a fundamental property of all cells. In higher eukaryotes, the small GTPase Cdc42, acting through a Par6-atypical protein kinase C (aPKC) complex, is required to establish cellular asymmetry during epithelial morphogenesis, asymmetric cell division and directed cell migration. However, little is known about what lies downstream of this complex. Here we show, through the use of primary rat astrocytes in a cell migration assay, that Par6-PKCzeta interacts directly with and regulates glycogen synthase kinase-3beta (GSK-3beta) to promote polarization of the centrosome and to control the direction of cell protrusion. Cdc42-dependent phosphorylation of GSK-3beta occurs specifically at the leading edge of migrating cells, and induces the interaction of adenomatous polyposis coli (Apc) protein with the plus ends of microtubules. The association of Apc with microtubules is essential for cell polarization. We conclude that Cdc42 regulates cell polarity through the spatial regulation of GSK-3beta and Apc. This role for Apc may contribute to its tumour-suppressor activity.read more
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Rho GTPases: Biochemistry and Biology
Aron B. Jaffe,Alan Hall +1 more
TL;DR: This review presents the best characterized of these biochemical pathways that control some of the most fundamental processes of cell biology common to all eukaryotes, including morphogenesis, polarity, movement, and cell division.
Journal ArticleDOI
Convergence of Wnt, ß-Catenin, and Cadherin Pathways
W. James Nelson,Roel Nusse +1 more
TL;DR: Evidence is assembled of possible interrelations between Wnt and other growth factor signaling, β-catenin functions, and cadherin-mediated adhesion in tissue differentiation.
Journal ArticleDOI
Mammalian Rho GTPases: new insights into their functions from in vivo studies.
Sarah J. Heasman,Anne J. Ridley +1 more
TL;DR: The recent availability of knockout mice for several members of the Rho family reveals new information about their roles in signalling to the cytoskeleton and in development.
Journal ArticleDOI
EMT, the cytoskeleton, and cancer cell invasion
TL;DR: This review has summarized recent novel insights into the molecular processes and players underlying EMT on one side and the formation of invasive membrane protrusions on the other side.
Journal ArticleDOI
The glamour and gloom of glycogen synthase kinase-3.
TL;DR: Much effort is currently directed towards understanding the functions and control of GSK3, and identifying methods capable of diminishing the deleterious impact of G SK3 in pathological conditions.
References
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Journal ArticleDOI
Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm
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Rho GTPases in cell biology.
TL;DR: Rho GTPases are molecular switches that control a wide variety of signal transduction pathways in all eukaryotic cells and their ability to influence cell polarity, microtubule dynamics, membrane transport pathways and transcription factor activity is probably just as significant.
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Leukocyte-endothelial cell recognition: Three (or more) steps to specificity and diversity
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Binding of GSK3β to the APC-β-Catenin Complex and Regulation of Complex Assembly
TL;DR: It is shown that when β-catenin is present in excess, APC binds to another component of the WINGLESS pathway, glycogen synthase kinase 3β (GSK3β), a mammalian homolog of Drosophila ZESTE WHITE 3, which was a good substrate for GSK3β in vitro and the phosphorylation sites were mapped to the central region of APC.