Date of Graduation
2007
Document Type
Thesis
Abstract
Significant evidence indicates the existence of cross-talk between PKCα, cSrc and PI3-kinase signaling pathways. Activation of each of these kinases results in substantial changes in actin filament concomitant with increased cell motility and invasive potential. The ability of PKCα to induce cSrc activation requires the adaptor protein, AFAP-110. This results in the disruption of the actin cytoskeleton and the formation of motility structures. Activation of PI3-kinase has been shown to direct up-regulation of PKCα activity. However the ability of PKCα to activate PI3-kinase remains controversial. Further, the integrity of the PH1 domain was required for PMA induced colocalization between AFAP-110 and cSrc, and PH domains are known to interact with PI3-kinase generated lipid products. In this work, we wanted to determine whether PI3-kinase signaling played a role in PMA induced colocalization between AFAP-110 and cSrc. Thus, we hypothesize that PKCα directs AFAP-110 to colocalize with cSrc in a manner dependent upon PI3-kinase activity, subsequently activating cSrc and directing changes in actin filament integrity. Chapter 1 of this dissertation was a literature review of cSrc, AFAP-110, PI3-kinase and PKCα signaling pathways. Chapter 2 examines the role of PI3-kinase activity in mediating the ability of AFAP-110 to active cSrc in response to PKCα activation. Chapter 3 discusses the ability of PI3-kinase activity to mediate AFAP-110 directed cSrc activation and podosome formation in response to PKCα activation. Chapter 4 examines the role of AFAP-110 in PI3-kinase mediated cell motility in ovarian cancer.
Recommended Citation
Walker, Valerie Glynis, "PI3-kinase mediates cSrc activation and podosome formation through the adaptor protein, AFAP-110, in response to PKCα activation." (2007). Graduate Theses, Dissertations, and Problem Reports. 9960.
https://researchrepository.wvu.edu/etd/9960